Article |
Address correspondence to Kathleen J. Green, Dept. of Pathology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: (312) 503-5300. Fax: (312) 503-8240. email: kgreen{at}northwestern.edu
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: Armadillo; adherens junction; N-cadherin; microtubule; trafficking
Abbreviations used in this paper: Arm, armadillo; JMD, juxtamembrane domain; KHC, kinesin heavy chain; KLC, kinesin light chain; MT, microtubule; p120, p120 catenin.
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
p120 is a member of the armadillo (Arm) supergene family (Reynolds et al., 1992; Peifer et al., 1994), and it was originally discovered as a substrate for Src (Reynolds et al., 1992) and various other tyrosine kinases (Downing and Reynolds, 1991; Kanner et al., 1991). p120 is composed of an NH2-terminal head domain, an ARM domain containing 10 Arm repeats and a short COOH-terminal tail (Anastasiadis and Reynolds, 2000). The Arm repeats are involved in the direct interaction of p120 to classical cadherins (Reynolds et al., 1996), whereas the functions of the NH2-terminal head domain and the COOH-terminal tail are not known.
The function of p120 in cellcell adhesion has remained controversial, as previous reports suggest that p120 can both positively and negatively regulate cadherin-mediated adhesion, likely depending on cellular context and the activity of specific signaling pathways. Several reports suggested that p120 might be required for clustering of cadherins and strong cellcell adhesion (Yap et al., 1998; Thoreson et al., 2000). In contrast, another paper indicated a role of p120 in the inhibition of cellcell adhesion in Colo205 cells (Aono et al., 1999). In human cancer cells deficient in p120 expression, p120 binding to cadherins stabilizes cadherins and restores their accumulation at cell borders (Ireton et al., 2002), which is consistent with genetic experiments in Drosophila and Caenorhabditis elegans supporting a positive regulatory role of p120 in cadherin function (Myster et al., 2003; Pettitt et al., 2003). Moreover, p120 has been shown to regulate the activity of Rho small GTPases (Anastasiadis et al., 2000; Noren et al., 2000; Grosheva et al., 2001) and thus influence cadherin-mediated cell adhesion and cell migration, but the exact mechanisms by which p120 regulates cadherin function and cellcell adhesion are still unclear.
The pivotal roles of cadherin-based junctions during development and tissue morphogenesis require the dynamic regulation of their assembly and function (Gumbiner, 2000). Several mechanisms may contribute to the regulation of cadherin-based adhesion (Gumbiner, 2000), including the cell surface delivery of junctional complexes and their turnover (Hinck et al., 1994; Le et al., 1999; Palacios et al., 2002). In neural crest cells, formation of stable intercellular adhesion results from the recruitment of N-cadherin from an intracellular pool rather than from a redistribution of surface-bound N-cadherins (Monier-Gavelle and Duband, 1995, 1997). Using GFP-tagged N-cadherin and time-lapse imaging, Mary et al. (2002) showed that N-cadherin transport to cell surface in fibroblasts is dependent on the formation of cellcell contact and requires the microtubule (MT) network and the MT-associated motor protein kinesin. However, it is not known how cadherin trafficking to the cell surface is regulated or which cadherin-associated proteins might be involved in this process.
Here, we provide evidence that p120 promotes the trafficking of cadherins to the cell surface via association and recruitment of kinesin. Our data reveal a novel role of p120 in the trafficking of cadherins, and suggest a mechanism by which the delivery of cadherins to the cell surface is specifically regulated by a catenin protein.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
To further examine whether the dynamics of p120-GFP particles were dependent on MTs, REF52 cells expressing p120-GFP were examined after treatment with nocodazole to disrupt the MT networks. Both the unidirectional translocation and structural changes were abolished by this treatment (Fig. 2 A'; Video 4, available at http://www.jcb.org/cgi/content/full/jcb.200305137/DC1). Some local random movements of p120-GFP were observed in the presence of nocodazole, which lacked the directionality of MT-dependent transport of vesicles, suggesting that they were caused by Brownian motion or MT-independent mechanisms.
|
p120 associates with conventional kinesin heavy chain
To investigate the role of p120 in the delivery of cadherins to the cell surface, we examined the possibility that p120 might associate with endogenous kinesin in REF52 cells. A subset of p120-GFP dots colocalized with kinesin as discrete dots in the cytoplasm, and kinesin was also recruited to cellcell contacts, where it colocalized with p120-GFP (Fig. 3 A). To test if p120 can physically associate with kinesin, we performed coimmunoprecipitation experiments from HEK293 cells cotransfected with p120 and conventional kinesin heavy chain (KHC) or kinesin light chain (KLC; Fig. 3 B). Virtually no p120 coimmunoprecipitated with KLC, whereas a small amount of p120 coimmunoprecipitated with KHC, indicating that p120 associates with kinesin through KHC.
|
To further analyze the association of p120 with kinesin, a series of GFP-tagged p120 constructs were used in coimmunoprecipitation experiments to test their ability to associate with KHC. p120N, but not p120
N2, lost the ability to associate with KHC (Fig. 4, A and B). The Arm repeats of p120 are required for cadherin binding, and p120
N2 has been shown previously to interact with cadherins (Reynolds et al., 1996). Coimmunoprecipitation experiments from cotransfected HEK293 cells confirmed that p120
N interacted with E-cadherin just as efficiently as full-length p120, but it no longer coimmunoprecipitated with KHC (Fig. 4 C). These data suggest that the association of p120 with kinesin is mediated by the p120 NH2-terminal head domain, but not the Arm-repeat domain, which is involved in p120 binding to cadherins.
|
Disruption of p120 binding to N-cadherin delays accumulation of N-cadherin at cellcell contacts during junction reassembly
An E-cadherin mutant deficient in p120 binding can still accumulate at cell borders (Thoreson et al., 2000; Ireton et al., 2002), indicating that p120 binding to cadherin tail is not absolutely required for the cell surface delivery of cadherins. However, our observations that p120 associates with kinesin and recruits it to cadherins suggest a positive role of p120 in facilitating the transport of cadherins to the cell surface. To investigate the involvement of p120 in cadherin trafficking, we generated N-cadYFP and N-cad AAA-YFP with a triple Ala mutation in its JMD domain. This triple Ala mutation in the cadherin JMD domain has been shown to specifically disrupt its interaction with p120 (Thoreson et al., 2000), and our coimmunoprecipitation experiments confirmed the loss of interaction between N-cad AAA-YFP and p120 (Fig. 5 A). Coexpression of N-cadYFP and p120-CFP in REF52 cells resulted in their extensive colocalization as cytoplasmic dots and at cell borders, whereas p120-CFP was mostly diffuse in the cytoplasm when coexpressed with N-cad AAA-YFP (unpublished data).
|
To further evaluate the physiological role of p120 in promoting the delivery of cadherins to the cell surface, we performed similar calcium switch experiments with REF52 cells transiently expressing only ectopic N-cadYFP or N-cad AAA-YFP, but not ectopic p120. Sequential detergent extraction and immunoblot showed that REF52 cells express endogenous kinesin and p120, and they are mainly distributed in the Triton-soluble membrane pool and the saponin-soluble cytosolic pool (Fig. 6 A). A major band of endogenous kinesin was recognized by two different anti-KHC antibodies. Both ectopic N-cadYFP and N-cad AAA-YFP localized at cell borders and in the cytoplasm 20 h after transfection, and 30 min of EGTA treatment disrupted their accumulation at cellcell contacts (Fig. 6 B). Within 30 min of calcium recovery, N-cadYFP relocalized efficiently to cellcell contact sites, whereas N-cad AAA-YFP still remained largely cytoplasmic with very little cell border accumulation. Consistent with a positive role for p120 in cadherin trafficking, the redistribution of N-cadYFP to cell borders was slower in the absence of ectopic p120 because we could not detect strong border accumulation of N-cadYFP after 15 min of calcium recovery without ectopic p120 (unpublished data). Quantification of adjacent pairs of transfected cells showed that the accumulation level of N-cadYFP at cell borders was on average 2.4-fold greater than that of N-cad AAA-YFP after 30 min of calcium recovery (Fig. 6 C). Because no ectopic p120 was expressed in these cells, the binding of the endogenous pool of p120 to cadherins is sufficient to promote their delivery to the cell surface, and introducing ectopic p120 to elevate the p120 level further accelerates this process (Fig. 5). Together, these data strongly support a physiological role of p120 in facilitating the accumulation of cadherins at cellcell contacts.
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Experiments in MDCK cells reported that shortly after its synthesis, E-cadherin forms a complex with ß-catenin and is then transported to the cell surface, where -catenin associates with the complex (Hinck et al., 1994). A more recent report demonstrated that ß-catenin,
-catenin, and p120 were all found in a complex with proN-cadherin in HeLa cells, but only p120 was associated with the earliest form of N-cadherin (Wahl et al., 2003), suggesting that proN-cadherin associates immediately with p120 after synthesis. This is consistent with our observation that some p120 colocalized with N-cadherin in the perinuclear Golgi region (Fig. 5). Together with our result showing the coincidence of p120 and N-cadherin dynamics (Fig. 1), these observations raise the possibility that p120 is involved throughout the process of transporting newly synthesized cadherins from the Golgi to the cell surface. It remains to be determined if p120 also regulates the exit of cadherins from the Golgi, or if it is only involved in the transport of cadherins along MTs. In the calcium switch model, EGTA treatment induces the disassembly of cellcell junctions and the endocytosis of cadherins, some of which are recycled back to the cell surface upon calcium restoration (Kartenbeck et al., 1982, 1991; Le et al., 1999; Mary et al., 2002). Therefore, it is possible that both the delivery of newly synthesized cadherins and the recycling of endocytosed cadherins contribute to the reaccumulation of cadherins at the cell surface after calcium recovery. p120 might facilitate both of these processes by recruiting kinesin to different subsets of cadherin-containing vesicles, and future experiments will be needed to address these questions.
Further insight into the in vivo functions of p120 came from several recent works examining the consequences of loss of p120 in Drosophila and C. elegans (Myster et al., 2003; Pettitt et al., 2003). In contrast to mammals, which express multiple isoforms of p120 and several p120-related proteins, Drosophila and C. elegans each have only a single p120 homologue. Loss of p120 function by genetic mutation or RNA interference revealed that p120 is not an essential component of adherens junctions in either organism, but loss of p120 greatly enhances the phenotypes caused by mutations in cadherins, ß-catenin, and -catenin. These results suggest that p120 plays a positive role in modulating cadherin functions, and its absence or reduced level leads to increased sensitivity toward disruption of cadherincatenin functions. The nonessential role of p120 in cadherin function in flies and worms is further supported by an experiment in which a Drosophila E-cadherin AAA mutant defective in p120 binding completely substituted for the activity of endogenous E-cadherin in a variety of cadherin-dependent processes (Pacquelet et al., 2003). However, these reports do not necessarily indicate that the role of mammalian p120 is also nonessential in cadherin functions. It is likely that the increased complexity of tissue organization and morphogenetic events has enabled p120 to evolve into a more important regulator of cellcell adhesion than its counterparts in flies and worms. This might be achieved through additional protein interactions and regulatory domains, as suggested by sequence comparisons of Drosophila and C. elegans p120 with mammalian p120 (Myster et al., 2003; Pettitt et al., 2003), which showed that they share little sequence homology outside of the Arm-repeat domain. Importantly, several putative proteinprotein interaction motifs and the phosphorylation domain in the NH2 terminus of mammalian p120 were not found in Drosophila and C. elegans p120. p120 associates with kinesin through its NH2 terminus, which shows great sequence diversity among different species; therefore, it will be very interesting to test if this is one of the conserved functions of p120 throughout evolution.
One of the most poorly understood aspects of MT-based trafficking is the identity of the cargo protein for each motor and the nature of the motorcargo interaction. Conventional kinesin is a heterotetramer composed of two KHCs and two KLCs. KHC contains three domains; an NH2-terminal motor domain, a central coiled-coil stalk region involved in dimerization, and a COOH-terminal globular tail domain (Vale and Fletterick, 1997; Diefenbach et al., 1998; Verhey et al., 1998). The tail region of the kinesin molecule, including the KHC COOH terminus and KLC, is most likely to be involved in cargo binding. Several transmembrane and cytoplasmic-binding partners of KHC and KLC have been reported (Karcher et al., 2002). Here, we identify p120 as a potential novel binding partner for KHC and a linker between kinesin and the transmembrane cadherin molecules. Whether this association between p120 and KHC is a direct interaction awaits further investigation, but the p120 NH2 terminus deletion mutant (p120N) loses its ability to associate with KHC while still being able to bind cadherins, suggesting that the association between p120 and KHC is not mediated by cadherins. Another recent report demonstrated a direct interaction between dynein and ß-catenin (Ligon et al., 2001), but we did not detect p120 associating with dynein by either coimmunoprecipitation or immunofluorescence (unpublished data). The ability of p120
N2 to associate with KHC implies that the binding site for KHC might lie within the first 27 aa, or the last 114 aa in the NH2 terminus immediately adjacent to the Arm-repeat domain of p120.
The relatively small amount of p120 coimmunoprecipitated with KHC from cotransfected cells suggests that this association must be a tightly regulated event that responds to proper positional and temporal signals. Several mechanisms might be involved in regulating the association between p120 and KHC, including association of KLC or other proteins with KHC, binding of p120 to cadherins, or post-translational modification of KHC or p120. p120 is a prominent Src substrate (Reynolds et al., 1992), and is tyrosine phosphorylated in response to activation of many receptor tyrosine kinases (Daniel and Reynolds, 1997). Interestingly, the NH2-terminal region immediately adjacent to the Arm-repeat domain of p120 encompasses a 100-aa phosphorylation domain that contains the majority of the tyrosine phosphorylation sites on p120 (Mariner et al., 2001), raising the possibility that tyrosine phosphorylation of p120 in the NH2 terminus regulates its association with kinesin.
The importance of p120 function is emphasized by a number of recent reports showing the loss of p120 expression in many types of tumors, and a correlation with poor prognosis in many cases (Thoreson and Reynolds, 2002). The identification of a new role of p120 in cadherin trafficking provides mechanistic insight into the functions of p120 in regulating junctional complex assembly, and is an important step toward understanding the dynamic nature of cellcell adhesion during cell migration and metastasis.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Cell culture and transfections
HEK293 cells were grown in DME supplemented with 10% FBS, 100 U/ml penicillin, and 100 µg/ml streptomycin (Mediatech). REF52 cells were grown in DME/Ham's F12 (50/50 mix) supplemented with 10% FBS, 100 U/ml penicillin, and 100 µg/ml streptomycin (Mediatech). For transient transfection of HEK293 cells, calcium phosphate transfection was performed as described previously (Stappenbeck and Green, 1992). REF52 cells were transfected using FuGENETM 6 reagent (Roche) according to the manufacturer's protocol and assayed 2024 h later.
Immunofluorescence
Immunofluorescence procedures have been previously described in detail (Chen et al., 2002). In brief, 2024 h after transfection, cells were washed in PBS, fixed in methanol for 2 min at -20°C, and incubated with appropriate primary and secondary antibodies for 30 min each at 37°C. Primary antibodies are as follows: p120 mouse monoclonal antibody used at 1:500 (Transduction Laboratories); anti-p120 rabbit polyclonal antibody F1-SH (provided by Dr. Al Reynolds, Vanderbilt University, Nashville, TN) used at 0.5 µg/ml; mouse monoclonal KHC antibody (H1) used at 1:100 (CHEMICON International). Alexa® Fluorconjugated goat antimouse or goat antirabbit secondary antibodies were used at 1:300 (Molecular Probes, Inc.). Images were obtained on a microscope (DMR; Leitz) using a digital camera (Orca; Hamamatsu) and Openlab imaging software (Improvision).
Time-lapse fluorescence microscopy
REF52 cells growing on glass-bottom dishes (World Precision Instruments) were transiently transfected. 4872 h later, the dish was mounted on an inverted microscope (Diaphot 300; Nikon) equipped with a Plan Fluor 100x, 1.30 NA oil objective and a slow-scan cooled CCD camera (model CH350; Photometrics). For GFP fusion protein imaging, fluorescent images were captured using a longpass filter set (Endow GFP; Chroma). For CFP/YFP double imaging, the lambda 102 optical filter changer (Sutter Instrument Company) was used with dual-band beamsplitters and single-band excitation/emission filters (Chroma Technology Corp.). Images were transferred to a computer workstation running MetaMorph® imaging software (Universal Imaging Corp.). Images were collected at 3-s intervals for 5 to 10 min. During live-cell imaging, temperature was kept at 33 ± 1°C by using flexible heaters (Omegalux) on the objective lens.
Coimmunoprecipitation, immunoblot, and sequential detergent extraction
Coimmunoprecipitation and immunoblot were performed as described in detail previously (Chen et al., 2002). Transfected HEK293 cells in 60-mm dishes were lysed with 500 µl ice-cold lysis buffer (1% Triton X-100, 145 mM NaCl, 10 mM Tris-HCl, pH 7.4, 5 mM EDTA, 2 mM EGTA, and 1 mM phenylmethylsulfonyl fluoride). Lysates were vortexed for 30 s and centrifuged at 12,000 rpm for 30 min at 4°C. The supernatant was transferred to a new tube, precleared with 40 µl GammaBind Plus Sepharose beads (Amersham Biosciences) for 1.5 h and centrifuged for 2 min to remove nonspecific complexes. Immunoprecipitation was performed using antibodies as follows: a mouse monoclonal anti-Myc antibody 9E10 (Sigma-Aldrich), a rat monoclonal anti-HA antibody 3F10 (Roche), and a rabbit polyclonal anti-GFP antibody that also recognizes YFP and CFP (CLONTECH Laboratories, Inc.). Immunoblots were performed using antibodies as follows: p120 mouse monoclonal antibody used at 1:1,000; anti-p120 rabbit polyclonal antibody F1-SH used at 1:3,440; mouse anti-KHC antibody (H2; CHEMICON International) used at 1:1,000; rabbit anti-KHC peptide antibody KHC13 used at 1:2,500 (a gift from Dr. Kristen J. Verhey, University of Michigan Medical School, Ann Arbor, MI; Verhey et al., 1998); mouse monoclonal anti-Myc antibody 9E10 used at 1:1,000 (Sigma-Aldrich); rat monoclonal anti-HA antibody 3F10 (Roche) used at 1:1,000; mouse monoclonal Living ColorsTM A.v. anti-GFP antibody JL-8 used at 1:4,000, and rabbit Living ColorsTM A.v. anti-GFP peptide antibody used at 1:100 (CLONTECH Laboratories, Inc.). Sequential detergent extraction was performed as described previously (Palka and Green, 1997), except that cells were grown in 6-well dishes and the amount of buffer used at each step was adjusted so that the final volume of each pool was 400 µl.
Coimmunoprecipitation from mouse brain high speed supernatant fraction in the absence of detergent was performed as described in detail previously (Verhey et al., 2001). For immunoprecipitation, 1 mg high speed supernatant was used, and 90 µg mouse anti-KHC antibody (H2; CHEMICON International) or nonspecific mouse IgG was added to the supernatant and incubated for 4 h at 4°C. The immunocomplexes were isolated with 60 µl GammaBind Plus Sepharose beads and analyzed by SDS-PAGE and immunoblotting.
Calcium switch experiment and quantification
2024 h after transfection, REF52 cells growing on glass coverslips were washed four times with PBS without calcium and magnesium and incubated in the growth medium containing 4 mM EGTA for 30 min at 37°C. Cells were then washed four times with the growth medium and incubated with it at 37°C for different period of time before being fixed in methanol. To quantify the N-cadGFP or N-cadYFP border/total intensity ratio in transfected REF52 cells, pairs of closely contacting cells expressing N-cadGFP or both N-cadYFP and p120-CFP were randomly selected. The region of the cellcell contact with N-cadGFP/YFP accumulation was selected and the average pixel intensity was measured for the selected region using the measurement tool of the Openlab imaging software (Improvision). The average total N-cadGFP/YFP intensity was measured by selecting the area covering both of the two contacting cells. Background intensity was measured by selecting an empty area and subtracted from the border intensity, and total intensity respectively before the border/total intensity ratio was calculated. Statistical analysis was performed using the t test.
Online supplemental material
Videos 15 correspond to still images shown in Fig. 1 and Fig. 2. For Videos 1, 2, and 4, REF52 cells were transfected with p120-GFP. For Video 3, REF52 cells were transfected with p120-CFP and N-cadYFP. For Video 5, REF52 cells were transfected with p120-CFP and YFP-tubulin. 4872 h after transfection, time-lapse movies of transfected cells were recorded. For Videos 1, 2, and 4, time-lapse images were taken at 3-s intervals and the movies are shown at 15 frames/s. For Videos 3 and 5 (double imaging), time-lapse images of the same fluorescent channel were taken at 6-s intervals, and the delay caused by switching to the second channel is 3 s. The adjacent CFP and YFP images were merged and the videos are shown at 7.5 frames/s. Online supplemental material available at http://www.jcb.org/cgi/content/full/jcb.200305137/DC1.
![]() |
Acknowledgments |
---|
This work was supported by National Institutes of Health (NIH) grants R01AR41836 and project 4 of PO1DE12328 to K.J. Green, and NIH grant R01GM25062 to G.G. Borisy.
Submitted: 28 May 2003
Accepted: 18 September 2003
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aberle, H., S. Butz, J. Stappert, H. Weissig, R. Kemler, and H. Hoschuetzky. 1994. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J. Cell Sci. 107:36553663.
Anastasiadis, P.Z., and A.B. Reynolds. 2000. The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell Sci. 113:13191334.
Anastasiadis, P.Z., S.Y. Moon, M.A. Thoreson, D.J. Mariner, H.C. Crawford, Y. Zheng, and A.B. Reynolds. 2000. Inhibition of RhoA by p120 catenin. Nat. Cell Biol. 2:637644.[CrossRef][Medline]
Aono, S., S. Nakagawa, A.B. Reynolds, and M. Takeichi. 1999. p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells. J. Cell Biol. 145:551562.
Brieher, W.M., and B.M. Gumbiner. 1994. Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps. J. Cell Biol. 126:519527.[Abstract]
Bronner-Fraser, M. 1993. Mechanisms of neural crest cell migration. Bioessays. 15:221230.[Medline]
Chen, X., S. Bonne, M. Hatzfeld, F. van Roy, and K.J. Green. 2002. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and ß-catenin signaling. J. Biol. Chem. 277:1051210522.
Daniel, J.M., and A.B. Reynolds. 1995. The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or -catenin. Mol. Cell. Biol. 15:48194824.[Abstract]
Daniel, J.M., and A.B. Reynolds. 1997. Tyrosine phosphorylation and cadherin/catenin function. Bioessays. 19:883891.[Medline]
Diefenbach, R.J., J.P. Mackay, P.J. Armati, and A.L. Cunningham. 1998. The C-terminal region of the stalk domain of ubiquitous human kinesin heavy chain contains the binding site for kinesin light chain. Biochemistry. 37:1666316670.[CrossRef][Medline]
Downing, J.R., and A.B. Reynolds. 1991. PDGF, CSF-1, and EGF induce tyrosine phosphorylation of p120, a pp60src transformation-associated substrate. Oncogene. 6:607613.[Medline]
Grosheva, I., M. Shtutman, M. Elbaum, and A.D. Bershadsky. 2001. p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion. J. Cell Sci. 114:695707.
Gumbiner, B.M. 1996. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 84:345357.[Medline]
Gumbiner, B.M. 2000. Regulation of cadherin adhesive activity. J. Cell Biol. 148:399404.
Hinck, L., I.S. Nathke, J. Papkoff, and W.J. Nelson. 1994. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J. Cell Biol. 125:13271340.[Abstract]
Hulsken, J., W. Birchmeier, and J. Behrens. 1994. E-cadherin and APC compete for the interaction with ß-catenin and the cytoskeleton. J. Cell Biol. 127:20612069.[Abstract]
Ireton, R.C., M.A. Davis, J. van Hengel, D.J. Mariner, K. Barnes, M.A. Thoreson, P.Z. Anastasiadis, L. Matrisian, L.M. Bundy, L. Sealy, et al. 2002. A novel role for p120 catenin in E-cadherin function. J. Cell Biol. 159:465476.
Jou, T.S., D.B. Stewart, J. Stappert, W.J. Nelson, and J.A. Marrs. 1995. Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex. Proc. Natl. Acad. Sci. USA. 92:50675071.[Abstract]
Kanner, S.B., A.B. Reynolds, and J.T. Parsons. 1991. Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells. Mol. Cell. Biol. 11:713720.[Medline]
Karcher, R.L., S.W. Deacon, and V.I. Gelfand. 2002. Motor-cargo interactions: the key to transport specificity. Trends Cell Biol. 12:2127.[CrossRef][Medline]
Kartenbeck, J., E. Schmid, W.W. Franke, and B. Geiger. 1982. Different modes of internalization of proteins associated with adhaerens junctions and desmosomes: experimental separation of lateral contacts induces endocytosis of desmosomal plaque material. EMBO J. 1:725732.[Medline]
Kartenbeck, J., M. Schmelz, W.W. Franke, and B. Geiger. 1991. Endocytosis of junctional cadherins in bovine kidney epithelial (MDBK) cells cultured in low Ca2+ ion medium. J. Cell Biol. 113:881892.[Abstract]
Le, T.L., A.S. Yap, and J.L. Stow. 1999. Recycling of E-cadherin: a potential mechanism for regulating cadherin dynamics. J. Cell Biol. 146:219232.
Ligon, L.A., S. Karki, M. Tokito, and E.L. Holzbaur. 2001. Dynein binds to ß-catenin and may tether microtubules at adherens junctions. Nat. Cell Biol. 3:913917.[CrossRef][Medline]
Mariner, D.J., P. Anastasiadis, H. Keilhack, F.D. Bohmer, J. Wang, and A.B. Reynolds. 2001. Identification of Src phosphorylation sites in the catenin p120ctn. J. Biol. Chem. 276:2800628013.
Mary, S., S. Charrasse, M. Meriane, F. Comunale, P. Travo, A. Blangy, and C. Gauthier-Rouviere. 2002. Biogenesis of N-cadherin-dependent cell-cell contacts in living fibroblasts is a microtubule-dependent kinesin-driven mechanism. Mol. Biol. Cell. 13:285301.
Monier-Gavelle, F., and J.L. Duband. 1995. Control of N-cadherin-mediated intercellular adhesion in migrating neural crest cells in vitro. J. Cell Sci. 108:38393853.
Monier-Gavelle, F., and J.L. Duband. 1997. Cross talk between adhesion molecules: control of N-cadherin activity by intracellular signals elicited by ß1 and ß3 integrins in migrating neural crest cells. J. Cell Biol. 137:16631681.
Myster, S.H., R. Cavallo, C.T. Anderson, D.T. Fox, and M. Peifer. 2003. Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component. J. Cell Biol. 160:433449.
Nollet, F., G. Berx, and F. van Roy. 1999. The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer. Mol. Cell Biol. Res. Commun. 2:7785.[CrossRef][Medline]
Noren, N.K., B.P. Liu, K. Burridge, and B. Kreft. 2000. p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J. Cell Biol. 150:567580.
Pacquelet, A., L. Lin, and P. Rorth. 2003. Binding site for p120/-catenin is not required for Drosophila E-cadherin function in vivo. J. Cell Biol. 160:313319.
Palacios, F., J.K. Schweitzer, R.L. Boshans, and C. D'Souza-Schorey. 2002. ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat. Cell Biol. 4:929936.[CrossRef][Medline]
Palka, H.L., and K.J. Green. 1997. Roles of plakoglobin end domains in desmosome assembly. J. Cell Sci. 110:23592371.
Peifer, M., S. Berg, and A.B. Reynolds. 1994. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 76:789791.[Medline]
Pettitt, J., E.A. Cox, I.D. Broadbent, A. Flett, and J. Hardin. 2003. The Caenorhabditis elegans p120 catenin homologue, JAC-1, modulates cadherin-catenin function during epidermal morphogenesis. J. Cell Biol. 162:1522.
Reynolds, A.B., L. Herbert, J.L. Cleveland, S.T. Berg, and J.R. Gaut. 1992. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors ß-catenin, plakoglobin and armadillo. Oncogene. 7:24392445.[Medline]
Reynolds, A.B., J.M. Daniel, Y.Y. Mo, J. Wu, and Z. Zhang. 1996. The novel catenin p120cas binds classical cadherins and induces an unusual morphological phenotype in NIH3T3 fibroblasts. Exp. Cell Res. 225:328337.[CrossRef][Medline]
Stappenbeck, T.S., and K.J. Green. 1992. The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. J. Cell Biol. 116:11971209.[Abstract]
Takeichi, M. 1995. Morphogenetic roles of classic cadherins. Curr. Opin. Cell Biol. 7:619627.[CrossRef][Medline]
Thoreson, M.A., and A.B. Reynolds. 2002. Altered expression of the catenin p120 in human cancer: implications for tumor progression. Differentiation. 70:583589.[CrossRef][Medline]
Thoreson, M.A., P.Z. Anastasiadis, J.M. Daniel, R.C. Ireton, M.J. Wheelock, K.R. Johnson, D.K. Hummingbird, and A.B. Reynolds. 2000. Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. J. Cell Biol. 148:189202.
Vale, R.D., and R.J. Fletterick. 1997. The design plan of kinesin motors. Annu. Rev. Cell Dev. Biol. 13:745777.[CrossRef][Medline]
Verhey, K.J., D.L. Lizotte, T. Abramson, L. Barenboim, B.J. Schnapp, and T.A. Rapoport. 1998. Light chain-dependent regulation of kinesin's interaction with microtubules. J. Cell Biol. 143:10531066.
Verhey, K.J., D. Meyer, R. Deehan, J. Blenis, B.J. Schnapp, T.A. Rapoport, and B. Margolis. 2001. Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152:959970.
Wahl, J.K., III, Y.J. Kim, J.M. Cullen, K.R. Johnson, and M.J. Wheelock. 2003. N-cadherin-catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane. J. Biol. Chem. 278:1726917276.
Wilson, A.J., and P.R. Gibson. 1997. Epithelial migration in the colon: filling in the gaps. Clin. Sci. (Lond.). 93:97108.[Medline]
Yap, A.S. 1998. The morphogenetic role of cadherin cell adhesion molecules in human cancer: a thematic review. Cancer Invest. 16:252261.[Medline]
Yap, A.S., C.M. Niessen, and B.M. Gumbiner. 1998. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. J. Cell Biol. 141:779789.