Correspondence to Yoshimi Takai: ytakai{at}molbio.med.osaka-u.ac.jp
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although the role of Necl-5 as PVR has been established, its physiological role remained unknown for a long time. We recently found that Necl-5 is functionally associated with integrin Vß3 at leading edges of moving cells, such as L cells stably expressing Necl-5 and NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells), and enhances the movement induced by growth factors, such as PDGF, in an integrin-dependent manner in NIH3T3 cells (Ikeda et al., 2004). Necl-5 enhances the growth factorinduced activation of Cdc42 and Rac, causing the formation of filopodia and lamellipodia, respectively, which eventually enhances cell movement. The cytoplasmic region of Necl-5 binds Tctex-1, a subunit of the dynein motor complex, which may be also involved in regulation of the cell movement in cooperation with microtubules (Mueller et al., 2002). Necl-5 enhances not only the cell movement but also the proliferation induced by growth factors, such as PDGF and FGF, in NIH3T3 cells (Kakunaga et al., 2004). Necl-5 enhances the activation of the RasRafMEKERK signaling and causes up- and down-regulation of the cell cycle regulators, including cyclins D2 and E and p27kip1, thereby shortening the period of the G1 phase of cell cycle. Necl-5 is up-regulated in V12Ras-NIH3T3 cells, and this up-regulation is mediated by the transcriptional activation of the Necl-5 gene through the V12RasRafMEKERKAP-1 pathway (Hirota et al., 2005). On the other hand, it has been shown that Necl-5 heterophilically trans-interacts with nectin-3 (Ikeda et al., 2003; Mueller and Wimmer, 2003), but the physiological function of the interaction of Necl-5 with nectin-3 remains unknown.
We describe here that the cellcell contact-induced interaction of Necl-5 with nectin-3 causes the endocytosis-mediated down-regulation of Necl-5 from the cell surface, resulting in reduction of cell movement and proliferation.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
We then performed knockdown of nectin-3 using the small interfering RNA (siRNA) method. Transfection of the synthetic siRNA against nectin-3 reduced the total amount of nectin-3 as estimated by Western blotting (Fig. 2 A, a). The total amount of nectin-1 or N-cadherin did not change (unpublished data). The amount of cell surface nectin-3, but not that of nectin-1 or N-cadherin, similarly decreased (Fig. 2 B, a). Immunofluorescence microscopy also showed that the signal for nectin-3 markedly decreased (Fig. 2 A, b1c2). The signal for N-cadherin did not change, which might be attributable to the presence of nectin-1. When the nectin-3 knockdown cells were cultured at the lower or higher density, the down-regulation of cell surface Necl-5 at the higher density markedly decreased as estimated by Western blotting (Fig. 2 B, a). Immunofluorescence microscopy showed that the cell surface signal for Necl-5 did not decrease in the nectin-3 knockdown cells cultured at the higher density (Fig. 2 B, b1c2). These results indicate that nectin-3 is a major molecule trans-interacting with Necl-5 and induces its down-regulation.
|
|
We then measured Necl-5 mRNA levels. Although the Necl-5 mRNA levels showed no obvious difference between the cells cultured at the lower and higher densities for 24 h (Fig. 1 E), they gradually decreased in a cell densitydependent manner when they were cultured for longer periods of time (Fig. 1 A, a, closed orange triangles). These results suggest that the cell densitydependent down-regulation of Necl-5 at the early stage is mainly mediated by endocytosis, although its down-regulation at the late stage is mediated by both endocytosis and transcriptional inactivation of the Necl-5 gene.
Clathrin-dependent endocytosis of Necl-5
There are at least two types of endocytosis: clathrin-dependent and -independent ones (Conner and Schmid, 2003). Epsin and Eps15 are regulatory components of the formation of clathrin-coated vesicles (Conner and Schmid, 2003), and the ENTH (epsin NH2-terminal homology domain) and the DIII domain of Eps15 act as dominant-negative (DN) mutants for the clathrin-dependent endocytosis (Benmerah et al., 1998; Nakashima et al., 1999). Dynamin is an important regulator for the formation of both clathrin-dependent and -independent endocytic vesicles, and its DN mutant, dynamin1 K44A, inhibits various types of endocytosis (Conner and Schmid, 2003). Caveolin regulates the formation of caveolae and its endocytosis, and an NH2-terminaltruncated mutant of caveolin, DGV-caveolin, serves as a DN mutant and inhibits the formation of caveolae by perturbing intracellular cholesterol trafficking (Conner and Schmid, 2003). To test whether or not the endocytosis of Necl-5 depends on clathrin, various DN mutants were expressed in NIH3T3 cells, and the cells were plated and cultured at the higher density. The nectin-3induced decrease of the cell surface signal for Necl-5 was inhibited by the expression of the myc-tagged epsin DN mutant (Fig. 4 A, a1a4, asterisks). The signal for nectin-3 did not change. The essentially similar results were obtained by the expression of the EGFP-tagged Eps15 DN mutant or HA-tagged dynamin DN mutant (Fig. 4 A, b1c4, asterisks). The nectin-3induced decrease of the cell surface signal for Necl-5 was not affected by the expression of the EGFP-tagged caveolin DN mutant (Fig. 4 A, d1d4, asterisks). These results indicate that Necl-5 is down-regulated by the clathrin-dependent endocytosis.
|
Reduction of cell movement and proliferation by the down-regulation of Necl-5
We next examined the effect of the down-regulation of Necl-5 on cell movement and proliferation. NIH3T3 cells, which were cultured at the lower or higher density in the presence or absence of the antiNecl-5 mAb-i, were replated, and cell movement after 9 h was assayed by the Boyden chamber method. In the absence of this mAb-i, the amount of cell surface Necl-5 and the degree of movement of NIH3T3 cells precultured at the higher density decreased in a roughly parallel manner as compared with those of the cells precultured at the lower density (Fig. 5 A, a and b). The decreases of these parameters were blocked by the mAb-i (Fig. 5 A, a and b). The level of Necl-5 down-regulated in the cells cultured at the higher density did not return to the original level at 9 h after replating at the lower density, but returned to the original level at 24 h (Fig. 5 A, b; and not depicted). The cells were cultured at the lower or higher density in the presence or absence of the mAb-i, and DNA synthesis was assayed by measuring the incorporation of BrdU. In the absence of this mAb-i, the amount of cell surface Necl-5 and the degree of DNA synthesis of NIH3T3 cells cultured at the higher density decreased in a roughly parallel manner (Fig. 5, A [b] and B [a, c, and e]). The decreases of these parameters were inhibited by the mAb-i (Fig. 5, A [b] and B [b, d, and e]). In the nectin-3 knockdown cells, the cell densitydependent decreases of cell movement and DNA synthesis were similarly inhibited (Fig. 6, A and B). The levels of this inhibition were roughly similar to those of the inhibition of the cell densitydependent down-regulation of cell surface Necl-5 (Fig. 2). In addition, when the cells were starved for 24 h and cultured in the presence of serum and the mAb-i, the growth rate did not markedly change, but the cell density rose to slightly higher than that of the cells cultured in the absence of the mAb-i after they became confluent (Fig. 1 A, a, open blue squares). These results indicate that the interaction of Necl-5 with nectin-3 causes the down-regulation of Necl-5, which subsequently reduces cell movement and proliferation.
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The cellcell contact-induced down-regulation of Necl-5 from the cell surface might be the result of its endocytosis, reduction of de novo synthesis, or both. We have shown here that the cell densitydependent down-regulation of Necl-5, at least at the early stage, is mainly mediated by clathrin-dependent endocytosis. Therefore, the interaction of Necl-5 with nectin-3 down-regulates Necl-5 through clathrin-dependent endocytosis. The detailed molecular mechanism of the endocytosis induced by the interaction of Necl-5 with nectin-3 is not known, but we have shown here that this interaction recruits the components necessary for the clathrin-dependent endocytosis, including clathrin heavy chain and adaptin ß, to the cytoplasmic region of Necl-5, which interacts with nectin-3. Therefore, the mechanism of endocytosis of Necl-5 is likely to be analogous to that of the endocytosis of cell surface receptors for hormones and cytokines, which are soluble molecules and coendocytosed with their respective membrane receptors upon their activation by hormones and cytokines. When Nef-3 is used as a ligand for Necl-5, it also serves as a soluble ligand for Necl-5 and is similarly coendocytosed with Necl-5. In contrast, nectin-3 is a transmembrane protein that trans-interacts with Necl-5 and is resistant to coendocytosis with Necl-5. One possible mechanism of the nectin-3induced endocytosis of Necl-5 is that the interaction of Necl-5 with nectin-3 causes the clustering of Necl-5, where the components of the clathrin-dependent endocytosis assemble and eventually form coated pits, followed by budding and pinching off of vesicles. In these processes, Necl-5, which interacts with nectin-3, may be replaced by nectin-1, resulting in the formation of free Necl-5, which is finally endocytosed, because the affinity of nectin-3 for nectin-1 is 10-fold higher than that of nectin-3 for Necl-5 (Ikeda et al., 2003). The interaction of nectin-3 with nectin-1 then induces the recruitment of N-cadherin there, resulting in the formation of adherens junctions. Another possible mechanism is that nectin-3, which interacts with Necl-5, is cleaved at the extracellular region and that its extracellular fragment is coendocytosed with Necl-5. Conversely, Necl-5, which interacts with nectin-3, may be cleaved at the extracellular region, and its extracellular fragment may be coendocytosed with nectin-3. However, the former possibility is less likely because cell surface nectin-3 did not decrease in a cell densitydependent manner.
When the cells were treated with Nef-3, the spotlike intracellular signal for Necl-5 increased and mostly colocalized with the signal for Rab7, which is a late endosomal marker. In contrast, this spotlike signal for Necl-5 was not observed in the cells cultured at the higher cell density in the absence of Nef-3, although the cell surface signal for Necl-5 markedly decreased. The exact reason for this apparent discrepancy is not known, but one possible explanation is that Necl-5 was endocytosed and transported to the late endosome in the cells cultured at the higher density in the absence of Nef-3 but its amount in the late endosome was too low to be detected. The other possible explanation is that when the cells were treated with Nef-3, Necl-5 was coendocytosed with Nef-3 and the Necl-5Nef-3 complex was delivered to the late endosome and was not further transported to the lysosome, where the proteins might be degraded, whereas Necl-5 free of nectin-3 was transported to the lysosome, where it was degraded in the cells cultured at the higher density in the absence of Nef-3.
We previously showed that Necl-5 has a potency to enhance cell movement and proliferation induced by growth factors such as PDGF and FGF (Ikeda et al., 2004; Kakunaga et al., 2004). Consistent with this finding, our current results show that the cellcell contact-induced down-regulation of Necl-5 causes reduction of cell movement and proliferation. The inhibition of this down-regulation by the antiNecl-5 mAb-i or the knockdown of nectin-3 blocks the reduction of cell movement and proliferation. The artificial knockdown of Necl-5 by the siRNA method similarly reduces cell movement and proliferation. Therefore, it is likely that the interaction of Necl-5 with nectin-3 causes the down-regulation of Necl-5, which then reduces cell movement and proliferation. As cultured cells become confluent, they form cellcell adhesion, gradually reducing and then finally stopping movement and proliferation (Abercrombie and Heaysman, 1953; Fisher and Yeh, 1967). This phenomenon has for a long time been known as contact inhibition of cell movement and proliferation, and several mechanisms have been reported. For instance, the vascular endothelial cadherinß-catenin complex inhibits the VEGF signaling for endothelial cell proliferation (Grazia Lampugnani et al., 2003); the E-cadherinmediated cellcell adhesion down-regulates extracellular regulated protein kinase signaling through the phosphoinositide 3-kinaseAkt pathway for cell proliferation (Laprise et al., 2004); the neurofibromatosis-2 gene product, merlin, and a transmembrane hyaluronic acid receptor, CD44, form a molecular switch that specifies cell growth arrest or proliferation (Morrison et al., 2001); and the effector of Rac/Cdc42, PAK1, and the PAK-interacting Rac-guanine nucleotide exchange factor, PIX, regulate contact inhibition during epithelial wound healing (Zegers et al., 2003). The present results that the cellcell contact-induced interaction of Necl-5 with nectin-3 and the subsequent endocytosis-mediated down-regulation of Necl-5 and reduction of cell movement and proliferation suggest that this mechanism is an additional mechanism for the contact inhibition of cell movement and proliferation. All the experiments shown here were performed by use of NIH3T3 cells, but essentially the same results were obtained for MEFs (see the online supplemental material and Figs. S1S5, available at http://www.jcb.org/cgi/content/full/jcb.200501090/DC1). Therefore, the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cellcell contacts is observed not only in NIH3T3 cells but also in MEFs.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Antibodies (Abs) and reagents
A rat IgG2a mAb against the extracellular region of Necl-5 (1A8-8, mAb-i) was prepared as described previously (Ikeda et al., 2003). A rabbit polyclonal Ab against the extracellular region of Necl-5 was used for Western blotting. Rabbit antinectin-1 pAb, rat antinectin-3 mAb, and rabbit antinectin-3
pAb were prepared as described previously (Satoh-Horikawa et al., 2000; Sakisaka et al., 2001). Hybridoma cells (9E10) expressing a mouse anti-myc mAb were purchased from American Type Culture Collection. A mouse antiN-cadherin mAb, mouse anticlathrin heavy chain mAb, and mouse adaptin ß mAb were purchased from BD Biosciences. A rabbit antiN-cadherin pAb was purchased from Takara. A mouse antiactin mAb was purchased from Chemicon. A mouse anti-HA mAb was purchased from Babco. A goat anti-Rab7 pAb was purchased from Santa Cruz Biotechnology, Inc. HRP-conjugated and fluorophore-conjugated secondary Abs were purchased from GE Healthcare, Chemicon, Jackson ImmunoResearch Laboratories, and ICN Biomedicals. DAPI was purchased from Nacalai Tesque. Nef-1 or -3 was prepared as described previously (Honda et al., 2003) and cross-linked by a rabbit antihuman IgG Fc pAb (Jackson ImmunoResearch Laboratories) before use.
pEFBOS-myc-epsin epsin NH2-terminal homology was supplied by A. Kikuchi (Hiroshima University, Hiroshima, Japan); pEGFP-Eps15 DIII by A. Benmerah (Cochin Institute, Paris, France); pCIneo-HA-dynamin1 K44A by S.L. Schmid (The Scripps Research Institute, La Jolla, California); pEGFP-DGV-caveolin by T. Fujimoto (Nagoya University, Nagoya, Japan); and pBS-H1 vector by H. Shibuya (Tokyo Medical and Dental University, Tokyo, Japan).
Immunofluorescence microscopy
The cells were fixed with 1% formaldehyde in PBS for 15 min and permeabilized with 100% methanol. Alternatively, the cells were fixed with acetone/methanol (1:1) for 1 min at 20°C. The cells, which were precultured with the antiNecl-5 mAb-i, were washed with a stripping buffer (0.2 M acetic acid and 0.5 M NaCl) before fixation. For blocking, the samples were incubated with 1% BSA in PBS and then with 20% BlockAce (Dainippon Seiyaku) in PBS. The samples were stained with the various combinations of the primary Abs and then with appropriate fluorophore-conjugated secondary Abs. The samples were analyzed using a confocal laser scanning microscope (Radiance 2000 or 2100; Bio-Rad Laboratories).
siRNA experiments
For the knockdown of nectin-3, double-stranded 25-nt RNA duplex, stealth RNA interference, to nectin-3 (5'-UGAUCAAUGUGCUGUUCAA-3') and control stealth RNA interference duplex were purchased from Invitrogen. Duplexes were transfected using Lipofectamine 2000 reagent according to the manufacturer's protocol. The transfection efficiency was monitored using FITC-labeled RNA oligo (Invitrogen). For the knockdown of Necl-5, the pBS-H1 vector containing H1 promoter was used for the expression of siRNA. To generate a vector for knockdown of Necl-5 (pBS-H1-Necl-5), a specific insert for Necl-5 was subcloned into pBS-H1. The insert was used as follows: mouse Necl-5 gene-specific insert was a 19-nt sequence corresponding to nt 767785 (5'-GGTATGTTGGCCTCACTAA-3') of mouse Necl-5 cDNA, which was separated by a 9-nt noncomplementary spacer (5'-TTCAAGAGA-3') from the reverse complement of the same 19-nt sequence. A pBS-H1 control vector had an insert including a 19-nt sequence (luciferase; 5'-CGTACGCGGAATACTTCGA-3') with no significant homology to any mammalian gene sequence. The cells were cotransfected with the pBS-H1 vector and the pEGFP-tub vector (CLONTECH Laboratories, Inc.) using Lipofectamine 2000 reagent. The EGFP-tubpositive cells were monitored as a marker of the cotransfection.
Boyden chamber assay
The Boyden chamber assay was performed as described previously (Ikeda et al., 2004), with some modifications. NIH3T3 cells were seeded at a density of 104 cells per insert. The cells were incubated at 37°C for 9 h in the presence of 10% serum. The migrated cells, which were stained with crystal violet or expressed EGFP-tub, were counted by phase contrast or fluorescence microscopic examination, respectively.
Other procedures
Cell growth assay and FACS analysis were performed as described previously (Kakunaga et al., 2004). Quantification of cell surface proteins and endocytosed Necl-5 by the biotinylation method were performed as described previously (Le et al., 1999). The endocytosis assay was performed at 18°C to inhibit recycling. Real-time RT-PCR was performed as described previously (Hirota et al., 2005). The levels of Necl-5 mRNA were determined as the absolute value to total RNA. Bead-cell adhesion assay using Nef-3coated latex beads was performed as described previously (Honda et al., 2003). The DNA synthesis assay was performed by using a BrdU labeling and detection kit I (Roche) according to the manufacturer's protocol.
Online supplemental material
Online supplemental text describes that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cellcell contacts is observed in MEFs. It also describes additional materials and methods for the experiments using MEFs. Fig. S1 shows that Necl-5 is down-regulated in a cell densitydependent manner in MEFs. Figs. S2 and S3 show that the cell densitydependent down-regulation of Necl-5 is induced by its interaction with nectin-3 in MEFs. Fig. S4 shows that Necl-5 is down-regulated by the clathrin-dependent endocytosis in MEFs. Fig. S5 shows that the down-regulation of Necl-5 reduces cell movement and proliferation in MEFs. Online supplemental material is available at http://www.jcb.org/cgi/content/full/jcb.200501090/DC1.
![]() |
Acknowledgments |
---|
Submitted: 18 January 2005
Accepted: 2 September 2005
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Abercrombie, M., and J.E. Heaysman. 1953. Observations on the social behaviour of cells in tissue culture. I. Speed of movement of chick heart fibroblasts in relation to their mutual contacts. Exp. Cell Res. 5:111131.[CrossRef][Medline]
Aoki, J., S. Koike, H. Asou, I. Ise, H. Suwa, T. Tanaka, M. Miyasaka, and A. Nomoto. 1997. Mouse homolog of poliovirus receptor-related gene 2 product, mPRR2, mediates homophilic cell aggregation. Exp. Cell Res. 235:374384.[CrossRef][Medline]
Benmerah, A., C. Lamaze, B. Begue, S.L. Schmid, A. Dautry-Varsat, and N. Cerf-Bensussan. 1998. AP-2/Eps15 interaction is required for receptor-mediated endocytosis. J. Cell Biol. 140:10551062.
Bottino, C., R. Castriconi, D. Pende, P. Rivera, M. Nanni, B. Carnemolla, C. Cantoni, J. Grassi, S. Marcenaro, N. Reymond, et al. 2003. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198:557567.
Chadeneau, C., B. LeMoullac, and M.G. Denis. 1994. A novel member of the immunoglobulin gene superfamily expressed in rat carcinoma cell lines. J. Biol. Chem. 269:1560115605.
Chadeneau, C., M. LeCabellec, B. LeMoullac, K. Meflah, and M.G. Denis. 1996. Over-expression of a novel member of the immunoglobulin superfamily in Min mouse intestinal adenomas. Int. J. Cancer. 68:817821.[CrossRef][Medline]
Conner, S.D., and S.L. Schmid. 2003. Regulated portals of entry into the cell. Nature. 422:3744.[CrossRef][Medline]
Feng, Y., B. Press, and A. Wandinger-Ness. 1995. Rab 7: an important regulator of late endocytic membrane traffic. J. Cell Biol. 131:14351452.[Abstract]
Fisher, H.W., and J. Yeh. 1967. Contact inhibition in colony formation. Science. 155:581582.[Medline]
Fuchs, A., M. Cella, E. Giurisato, A.S. Shaw, and M. Colonna. 2004. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J. Immunol. 172:39943998.
Grazia Lampugnani, M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T.O. Daniel, and E. Dejana. 2003. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, ß-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161:793804.
Gromeier, M., S. Lachmann, M.R. Rosenfeld, P.H. Gutin, and E. Wimmer. 2000. Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc. Natl. Acad. Sci. USA. 97:68036808.
Hirota, T., K. Irie, R. Okamoto, W. Ikeda, and Y. Takai. 2005. Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway. Oncogene. 24:22292235.[CrossRef][Medline]
Honda, T., K. Shimizu, T. Kawakatsu, M. Yasumi, T. Shingai, A. Fukuhara, K. Ozaki-Kuroda, K. Irie, H. Nakanishi, and Y. Takai. 2003. Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion. Genes Cells. 8:5163.
Ikeda, W., S. Kakunaga, S. Itoh, T. Shingai, K. Takekuni, K. Satoh, Y. Inoue, A. Hamaguchi, K. Morimoto, M. Takeuchi, et al. 2003. Tage4/nectin-like molecule-5 heterophilically trans-interacts with cell adhesion molecule nectin-3 and enhances cell migration. J. Biol. Chem. 278:2816728172.
Ikeda, W., S. Kakunaga, K. Takekuni, T. Shingai, K. Satoh, K. Morimoto, M. Takeuchi, T. Imai, and Y. Takai. 2004. Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, nectin-3-independent manner. J. Biol. Chem. 279:1801518025.
Kakunaga, S., W. Ikeda, T. Shingai, T. Fujito, A. Yamada, Y. Minami, T. Imai, and Y. Takai. 2004. Enhancement of serum- and platelet-derived growth factor-induced cell proliferation by Necl-5/Tage4/poliovirus receptor/CD155 through the Ras-Raf-MEK-ERK signaling. J. Biol. Chem. 279:3641936425.
Koike, S., H. Horie, I. Ise, A. Okitsu, M. Yoshida, N. Iizuka, K. Takeuchi, T. Takegami, and A. Nomoto. 1990. The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J. 9:32173224.[Abstract]
Laprise, P., M.J. Langlois, M.J. Boucher, C. Jobin, and N. Rivard. 2004. Down-regulation of MEK/ERK signaling by E-cadherin-dependent PI3K/Akt pathway in differentiating intestinal epithelial cells. J. Cell. Physiol. 199:3239.[CrossRef][Medline]
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.
Masson, D., A. Jarry, B. Baury, P. Blanchardie, C. Laboisse, P. Lustenberger, and M.G. Denis. 2001. Overexpression of the CD155 gene in human colorectal carcinoma. Gut. 49:236240.
Mendelsohn, C.L., E. Wimmer, and V.R. Racaniello. 1989. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 56:855865.[CrossRef][Medline]
Morrison, H., L.S. Sherman, J. Legg, F. Banine, C. Isacke, C.A. Haipek, D.H. Gutmann, H. Ponta, and P. Herrlich. 2001. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15:968980.
Mueller, S., and E. Wimmer. 2003. Recruitment of Nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to vß3 integrin containing membrane microdomains. J. Biol. Chem. 278:3125131260.
Mueller, S., X. Cao, R. Welker, and E. Wimmer. 2002. Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. J. Biol. Chem. 277:78977904.
Nakashima, S., K. Morinaka, S. Koyama, M. Ikeda, M. Kishida, K. Okawa, A. Iwamatsu, S. Kishida, and A. Kikuchi. 1999. Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. EMBO J. 18:36293642.
Sakisaka, T., T. Taniguchi, H. Nakanishi, K. Takahashi, M. Miyahara, W. Ikeda, S. Yokoyama, Y.F. Peng, K. Yamanishi, and Y. Takai. 2001. Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1. J. Virol. 75:47344743.
Sato, T., K. Irie, T. Ooshio, W. Ikeda, and Y. Takai. 2004. Involvement of heterophilic trans-interaction of Necl-5/Tage4/PVR/CD155 with nectin-3 in formation of nectin- and cadherin-based adherens junctions. Genes Cells. 9:791799.
Satoh-Horikawa, K., H. Nakanishi, K. Takahashi, M. Miyahara, M. Nishimura, K. Tachibana, A. Mizoguchi, and Y. Takai. 2000. Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J. Biol. Chem. 275:1029110299.
Shingai, T., W. Ikeda, S. Kakunaga, K. Morimoto, K. Takekuni, S. Itoh, K. Satoh, M. Takeuchi, T. Imai, M. Monden, and Y. Takai. 2003. Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/ SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells. J. Biol. Chem. 278:3542135427.
Sloan, K.E., B.K. Eustace, J.K. Stewart, C. Zehetmeier, C. Torella, M. Simeone, J.E. Roy, C. Unger, D.N. Louis, L.L. Ilag, and D.G. Jay. 2004. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration. BMC Cancer. 4:73.[CrossRef][Medline]
Takai, Y., and H. Nakanishi. 2003. Nectin and afadin: novel organizers of intercellular junctions. J. Cell Sci. 116:1727.
Takai, Y., K. Irie, K. Shimizu, T. Sakisaka, and W. Ikeda. 2003. Nectins and nectin-like molecules: roles in cell adhesion, migration, and polarization. Cancer Sci. 94:655667.[Medline]
Zegers, M.M., M.A. Forget, J. Chernoff, K.E. Mostov, M.B. ter Beest, and S.H. Hansen. 2003. Pak1 and PIX regulate contact inhibition during epithelial wound healing. EMBO J. 22:41554165.
|
|