A novel diuretic hormone receptor in Drosophila: evidence for conservation of CGRP signaling
1 Department of Anatomy and Neurobiology, Washington University School of
Medicine, St. Louis, MO 63110, USA
2 Department of Biochemistry, Cell and Molecular Biology, University of
Tennessee, Knoxville, TN 37996, USA
3 Department of Biochemistry, University of Nevada, Reno, NV 89557,
USA
4 Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU,
UK
Author for correspondence (e-mail:
taghertp{at}pcg.wustl.edu)
Accepted 1 February 2005
![]() |
Summary |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: G protein-coupled receptor, diuretic hormone-31, RCP, Drosophila
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To investigate mechanisms of peptide hormone signaling, we have searched
for receptors for these different diuretic hormones. The complete annotation
of the Drosophila genome (Adams et
al., 2000) has facilitated the identification of many G
protein-coupled receptors (GPCRs; Brody and
Cravchik, 2000
). A comprehensive phylogenetic analysis predicts
that 44 have neuropeptide ligands and that they share close ancestry with
mammalian receptor families (Hewes and
Taghert, 2001
). Of these 44 receptors, 39 belong to the rhodopsin
receptor family (Family A) while five are members of the secretin receptor
family (Family B; Hewes and Taghert,
2001
). Significant progress has been made with the assignment of
peptide ligands for Family A receptors, as more than half of these receptors
have been functionally characterized. However, of the five Drosophila
Family B peptide receptors, only one has been successfully identified: CG8422,
which is related to mammalian CRF-R and other insect DH receptors
(Reagan, 1994
), is a
functional DH44 receptor
(Johnson et al., 2004
).
We have studied the Drosophila orphan GPCR named CG17415, which is
most related to the mammalian receptor called CLR
(Hewes and Taghert, 2001). In
mammals, calcitonin-gene related peptide (CGRP) and adrenomedullin (AM) both
activate CLR, but their activities are defined by the co-expression of
specific accessory protein sub-types called RAMPs (receptor activity modifying
proteins; McLatchie et al.,
1998
; Buhlmann et al.,
1999
; Christopoulos et al.,
1999
; Hay et al.,
2004
). In addition, the receptor component protein (RCP) accessory
protein (Evans et al., 2000
)
is critical for downstream signaling from the CLR/RAMP complex. Here, we show
that the Drosophila neuropeptide DH31 is a potent ligand
for CG17415 and that CLR accessory proteins are also required for this
activity.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Immunocytochemistry
A synthetic peptide corresponding to a region of the second extracellular
loop of the predicted CG17415 protein (RGLGGTPEDNRHCW) was used to generate
rabbit antisera. A synthetic peptide corresponding to a region of the
C-terminal tail of the predicted CG8422 protein (TKSFSKGGGSPRAE) was used to
generate rabbit antisera (Genosphere, Paris, France). Immunocytochemistry was
performed on whole-mount tissues of Drosophila melanogaster adults
and third instar larvae of two control stocks, y w and Canton S.
Tissues were fixed for 3060 min at room temperature in 4%
paraformaldehyde in PBS, containing 7% picric acid (v/v). The tissues were
then washed and incubated in primary antibody for 48 h at 4°C, washed and
incubated with secondary antibody for 24 h at 4°C. In addition, staining
was performed on flies with GAL4-labeled neuronal subsets: peptidergic and
corazonin neurons were labeled in larvae and adult CNS, respectively, from
progeny of the cross y w; P{GAL4}c929 or y
w; P{GAL4}CRZ crossed to y w;
UAS-lacZ. For immunocytochemistry of Malpighian tubules, we used the
P{GAL4}c724::GAL4 driver to specifically label the
stellate cells (Sozen et al.,
1997). Tissues were incubated with anti-CG17415 (at 1:1000),
anti-CG8422 (at 1:1000), and/or mouse anti-ß-galactosidase (Promega Co.,
Madison WI, USA; diluted 1:1000). We used either Cy3-tagged or Alexa
488-tagged secondary antisera. Images were obtained on a Bio-Rad confocal
microscope and edited for contrast in Photoshop.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
To identify factors present in NIH 3T3 cells that permitted CG17415
activation, we reasoned that such signaling might be dependent on the
expression of other proteins, such as RAMPS and RCP
(McLatchie et al., 1998;
Buhlmann et al., 1999
;
Christopoulos et al., 1999
).
The Drosophila gene CG4875 encodes a probable homolog of
RCP, whereas no homologs of RAMPs have yet been identified in the
Drosophila genome. Co-expression of dRCP with the CG17415
receptor in HEK-293 cells conferred signaling properties in response
to DH31 (Fig. 1B).
Specifically, 1 µmol l1 DH31 produced a nearly
twofold increase in levels of the CRE-luc reporter, but again no
responses were recorded to any other of 22 peptides tested (data not
shown).
To extend this finding, we systematically co-expressed both the
Drosophila and human RCPs alone, or in combination with human RAMPs
in HEK-293 cells, and tested the CG17415 receptor pharmacological profile. We
found that both human RCP (Fig.
1C) and RAMPs (Fig.
2) permitted CG17415 receptor signals elicited by the
DH31 peptide; on average, signals following co-expression of
mammalian accessory proteins were approx. fivefold greater than seen with
co-expression of dRCP (Table
1). We then tested the possibility that alternative ligands may
activate the CG17415 receptor, depending on accessory protein expression
(McLatchie et al., 1998;
Buhlmann et al., 1999
;
Christopoulos et al., 1999
).
Specificity to DH31 was unaltered by expression of RAMP subtype
(Fig. 2). Additionally,
expression of RAMP1 or RAMP2 did not alter the pharmacological profile we
previously established for another Drosophila receptor (CG8422,
DH44-R1) (not shown), which is responsive to a CRF-like diuretic hormone
(DH44; Johnson et al.,
2004
).
|
|
We next asked whether desensitization of the CG17415 receptor was also
dependent upon the co-expression of these accessory subunits, as is the case
for mammalian CGRP receptors (Hilairet et
al., 2001). We found that ß-arrestin2-GFP translocation to
the membrane, which is a molecular event that is correlated with the process
of desensitization (Barak et al.,
1997
), was evident in a number of cells co-expressing these
receptor subunits following exposure to desensitizing doses of DH31
(Fig. 3). Moreover, we found
that the pattern of ß-arrestin2 association is typical of Family B
receptors, in that ß-arrestin2 is internalized following agonist
treatment, as indicated by the formation of fluorescently labeled vesicles
(Oakley et al., 2001
;
Tohgo et al., 2003
;
Johnson et al., 2003b
).
However, the incidence of translocation was only
5% of GFP-expressing
cells. We interpret this as indicative of the low number of cells that
effectively expressed the entire complement of four necessary transfected
components (receptor, two accessory proteins and arrestin-GFP). Additionally,
no other peptide tested was able to induce ß-arrestin2-GFP recruitment.
On this basis, we concluded the CG17415 receptor is a DH31
receptor, and hereafter we refer to it as DH31-R1.
|
Next, we assessed the tissue distribution of the DH31-R1 and DH44-R1 receptors using antibodies generated against receptor peptide epitopes. We first evaluated the staining properties of the antibodies in HEK-293 cells that were transiently transfected with either DH31-R1 or DH44-R1 cDNAs. For both antisera, specific staining was only evident on cells transfected with the homologous receptor DNA (Fig. S1 in supplementary material). In native tissues, we found DH31-R1 immunosignals in the principal cells of both larval and adult Malpighian tubules (Fig. 4). Within the larval CNS, both receptor antisera stained a small number of neurons: there are approximately 58 DH31-R1-positive neurons and approximately 24 DH44-R1-positive neurons in the brain and ventral nerve cord (VNC) (Fig. 5 and Fig. S1 in supplementary material). Based on similarities in these patterns, we tested for possible coincidence of DH receptor expression: remarkably, we found that all DH44-R1-positive neurons also expressed the DH31-R1 in the larval CNS. We first showed that all DH44-R1-positive cells expressed the neuropeptide corazonin (CRZ, as indicated by CRZ-GAL4 activity). We then found that all CRZ neurons also expressed DH31-R1 as well. At least one additional DH31-R1-positive population did not express DH-44-R1. Within the adult, several somata in the dorsal part of the brain are labeled by both receptor antisera (Fig. 6), and both receptor antisera also revealed receptor-specific cell groups as well. As in the larva, we found that all CRZ-positive neurons in the adult CNS were co-labeled by both DH31-R and DH44-R1 antibodies. For DH31-R, we observed an additional two to four cells that were neither CRZ- nor DH44-R1-positive, and approximately six DH44-R1-positive cells that did not express DH31-R1 or CRZ.
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
When expressed in NIH 3T3 cells, CG17415 did respond to DH31
without co-transfection of RCP or RAMPs; this can be attributed to higher
endogenous levels of RCP and RAMPs (Prado
et al., 2002). How CLR accessory proteins such as RCP and RAMPs
promote CLR functions remains uncertain; RCP may couple the receptor to the
Gs protein, or it may activate adenylate cyclase directly
(Prado et al., 2002
). In
mammals, RCP expression largely mirrors that of CLR
(Ma et al., 2003
), whereas
RAMP expression typically exceeds that of CLR. Consistent with the expectation
that RAMPs have a larger set of functions than does RCP, RAMPs interact with
more than the CLR receptor and are known to interact with the VPAC-1, PTH-1
receptor and glucagon receptor
(Christopoulos et al., 2003
).
We found that RAMP co-expression permitted detection of CG17415 receptor
activity without affecting its pharmacological profile. A comparable situation
occurs for the neuropeptide intermedin (also referred to as adrenomedullin 2;
Takei et al., 2004
), which is
related to CGRP. RAMP co-expression with CLR in HEK cells permitted functional
responses, but RAMP subtype did not alter the pharmacological response of the
CLR to intermedin (Roh et al.,
2004
).
The current lack of RAMP candidates in the Drosophila genome indicates either their true absence, or that diagnostic structural characteristics of RAMPs have not been conserved. Our results show that the Drosophila CLR is able to interact functionally with human RAMPs in HEK cells and we therefore consider it possible that Drosophila utilizes RAMP-like proteins. Given the promiscuity that many members of Family B receptors demonstrate for different ligands, we can neither rule out the possibility of additional peptide ligands for this receptor (which may be dependent upon a Drosophila RAMP), nor can we rule out additional DH31 receptors. We note there are two remaining orphan CLR-related receptors in the Drosophila genome (CG4395 and CG13758).
Another similarity between Drosophila CG17415 and the mammalian
CLR is that they both appear to require the RCP and RAMP accessory subunits
for desensitization as well as for signaling
(Hilairet et al., 2001;
Kuwasako et al., 2000
). While
the demonstration of CG17415 desensitization (indirectly measured by the
recruitment of ß-arrestin-GFP) may not be indicative of the situation
occurring in native cells, it does represent an additional measure of specific
receptor activation by the DH31 peptide. The pattern of
ß-arrestin2 association we observed is typical for a Family B receptor
(Oakley et al., 2000
;
Johnson et al., 2003b
).
The immunocytochemical demonstration of DH31-R expression in the principal
cells of the Malpighian tubules also supports the identification of
DH31 as a ligand. A recent study using microarray analysis
corroborates this finding; CG17415 transcript levels are enriched 17-fold
within the tubule (Wang et al.,
2004). We were unable to detect DH44-R1 immunosignals within the
principal cells of the tubule (data not shown), which is consonant with the
transcriptional profile of this tissue
(Wang et al., 2004
). A
potential second DH44 receptor that could mediate DH44
activation of cAMP on the tubule is encoded by CG12370
(Hewes and Taghert, 2001
;
Wang et al., 2004
). We note
that in our functional assays (Table
1) the estimates of EC50 values are larger than values derived
from physiological assays on DH31 sensitivity on isolated
Malpighian tubules (Furuya et al.,
2000
; Coast et al.,
2001
). However, the finding that human RCPs and RAMPs supported
uniformly larger amplitude responses (compared to the effect of co-expressed
Drosophila RCP) leads us to suggest that such differences probably
derive from issues of expression in a heterologous (e.g. mammalian) cellular
context. We think it is possible that the human accessory proteins are better
able to couple with downstream effectors in a human cell line than in the
Drosophila accessory protein. Thus, we argue that the
Drosophila RCP probably represents a fundamental component of in
vivo DH31 signaling.
The co-expression of DH31 (CG17415) and DH44 (CG8422)
receptors within CRZ neurons suggests clear, functional hypotheses
(Fig. 7). First, it indicates
that both the DH31 and DH44 signaling pathways play
unexpected roles to facilitate or inhibit CRZ release. Second, the fact that
all CRZ neurons express both receptors indicates a close association between
CRZ signaling functions and upstream regulation by convergent DH31
and DH44 signaling pathways. Third, the fact that a large fraction
of DH receptor-positive neurons are CRZ cells suggests that much of the DH
receptor signaling within the Drosophila CNS is dedicated to
regulation of CRZ release. Recent work has shown a co-localization of
different diuretic peptides in various insects
(Chen et al., 1994). In
Drosophila, DH44 is strictly co-localized with the
leucokinin receptor (Cabrero et al.,
2002
; Radford et al.,
2002
). That observation reinforces the general conclusion that the
functional interactions between these diuretic regulatory peptides in the
periphery may have counterparts within neural circuits of the CNS. Whether the
CRZ-expressing neurons contribute to the neural control of diuresis, or are
involved in unrelated physiology, is uncertain. Corazonin is a
multi-functional peptide that helps initiate ecdysis; is expressed in clock
neurons in Manduca (Wise et al.,
2002
; Kim et al.,
2004
), is correlated with pigmentation state in Locusta
(Tawfik et al., 1999
) and is
cardioactive in Periplaneta
(Veenstra, 1989
).
|
A convergence of CLR (DH31) receptor and CRF (DH44)
receptor signaling within functional neural circuits is not unprecedented.
These two signaling pathways coincide at several distinct loci within the
mammalian CNS and pituitary. For example, in the vestibular cerebellar cortex
of mice, CGRP and CRF-like immunostaining innervate non-overlapping domains of
Purkinje cell dendrites during development
(Yamano and Tohyama, 1994).
CRF mediates the CGRP-induced increase in corticosterone release
(Kovacs et al., 1995
).
Likewise, CRF helps mediate the CGRP suppression of pulsatile LH secretion via
gonadotropin releasing hormone (GnRH) neurons
(Li et al., 2004
). We note
that the receptor for the CRZ neuropeptide is ancestrally related to GnRH
receptors (Hewes and Taghert,
2001
; Park et al.,
2002
). CGRP terminals from pontine/parabrachial nucleus innervate
CRF neurons of the amygdyla, and both peptides in this pathway cause increases
in autonomic outflow, including increases in heart rate and blood pressure
(Kovacs et al., 1995
). This
detail is also notable since CRZ is a cardioactive factor
(Veenstra, 1989
). Together,
these observations are consistent with the hypothesis that the convergence of
CLR and CRF-R signaling pathways is a conserved feature in the evolution of
neural circuits. Further study of these signaling pathways in
Drosophila may therefore contribute to a fundamental understanding of
the peptide circuits across phylogeny.
![]() |
Acknowledgments |
---|
![]() |
Footnotes |
---|
* Present address: Department of Biology, Wake Forest University,
Winston-Salem, NC 27109, USA
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A.,
Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins,
R. A., Galle, R. F. et al. (2000). The genome sequence of
Drosophila melanogaster. Science
287,2185
-2195.
Barak, L. S., Ferguson, S. S., Zhang, J. and Caron, M. G.
(1997). A beta-arrestin/green fluorescent protein biosensor for
detecting G protein-coupled receptor activation. J. Biol.
Chem. 272,27497
-27500.
Brody, T. and Cravchik, A. (2000). Drosophila melanogaster G protein-coupled receptors. J. Cell. Biol. 150,F83 -F88.[Medline]
Buhlmann, N., Leuthauser, K., Muff, R., Fischer, J. A. and Born,
W. (1999). A receptor activity modifying protein
(RAMP)2-dependent adrenomedullin receptor is a calcitonin gene-related peptide
receptor when coexpressed with human RAMP1.
Endocrinology 140,2883
-2890.
Cabrero, P., Radford, J. C., Broderick, K. E., Costes, L., Veenstra, J. A., Spana, E. P., Davies, S. A. and Dow, J. A. (2002). The Dh gene of Drosophila melanogaster encodes a diuretic peptide that acts through cyclic AMP. J. Exp. Biol. 205,3799 -3807.[Medline]
Chen, Y., Veenstra, J. A., Hagedorn, H. and Davies, N. T. (1994). Leucokinin and diuretic hormone immunoreactivity of neurons in the tobacco hornworm, Manduca sexta, and co-localization of this immunoreactivity in lateral neurosecretory cells of abdominal ganglia. Cell Tissue Res. 278,493 -507.[CrossRef][Medline]
Christopoulos, A., Christopoulos, G., Morfis, M., Udawela, M.,
Laburthe, M., Couvineau, A., Kuwasako, K., Tilakaratne, N. and Sexton,
P. M. (2003). Novel receptor partners and function of
receptor activity-modifying proteins. J. Biol. Chem.
278,3293
-3297.
Christopoulos, G., Perry, K. J., Morfis, M., Tilakaratne, N.,
Gao, Y., Fraser, N. J., Main, M. J., Foord, S. M. and Sexton, P. M.
(1999). Multiple amylin receptors arise from receptor
activity-modifying protein interaction with the calcitonin receptor gene
product. Mol. Pharmacol.
56,235
-242.
Coast, G. M. (1996). Neuropeptides implicated in the control of diuresis in insects. Peptides 17,327 -336.[CrossRef][Medline]
Coast, G. M., Webster, S. G., Schegg, K. M., Tobe, S. S. and Schooley, D. A. (2001). The Drosophila melanogaster homologue of an insect calcitonin-like diuretic peptide stimulates V-ATPase activity in fruit fly Malpighian tubules. J. Exp. Biol. 204,1798 -1804.
Davies, S. A., Huesmann, G. R., Maddrell, S. H., O'Donnell, M. J., Skaer, N. J., Dow, J. A. and Tublitz, N. J. (1995). CAP2b, a cardioacceleratory peptide, is present in Drosophila and stimulates tubule fluid secretion via cGMP. Am. J. Physiol. 269,R1321 -R1326.[Medline]
Dow, J. T. and Davies, S. A. (2003).
Integrative physiology and functional genomics of epithelial function in a
genetic model organism. Physiol. Rev.
83,687
-729.
Dubos, M. P., Badariotti, F., Rodet, F., Lelong, C. and Favrel, P. (2003). Molecular and physiological characterization of an invertebrate homologue of a calcitonin-related receptor Biochem. Biophys. Res. Commun. 310,972 -978.[CrossRef][Medline]
Evans, B. N., Rosenblatt, M. I., Mnayer, L. O., Oliver, K. R.
and Dickerson, I. M. (2000). CGRP-RCP, a novel protein
required for signal transduction at calcitonin gene-related peptide and
adrenomedullin receptors. J. Biol. Chem.
275,31438
-31443.
Furuya, K., Milchak, R. J., Schegg, K. M., Zhang, J., Tobe, S.
S., Coast, G. M. and Schooley, D. A. (2000). Cockroach
diuretic hormones: characterization of a calcitonin-like peptide in insects.
Proc. Natl. Acad. Sci. USA
97,6469
-6474.
Hay, D. L., Conner, A. C., Howitt, S. G., Smith, D. M. and Poyner, D. R. (2004). The pharmacology of adrenomedullin receptors and their relationship to CGRP receptors. J. Mol. Neurosci. 22,105 -113.[CrossRef][Medline]
Hewes, R. and Taghert, P. (2001). Neuropeptides
and neuropeptide receptors in the Drosophila melanogaster genome.
Genome Res. 11,1126
-1142.
Hilairet, S., Belanger, C., Bertrand, J., Laperriere, A., Foord,
S. M. and Bouvier, M. (2001). Agonist-promoted
internalization of a ternary complex between calcitonin receptor-like
receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.
J. Biol. Chem. 276,42182
-42190.
Hill, C. A., Fox, A. N., Pitts, R. J., Kent, L. B., Tan, P. L.,
Chrystal, M. A., Cravchik, A., Collins, F. H., Robertson, H. M. and
Zwiebel, L. J. (2002). G protein-coupled receptors in
Anopheles gambiae. Science
298,176
-178.
Johnson, E. C., Garczynski, S. F., Park, D., Crim, J. W.,
Nassel, D. R. and Taghert, P. H. (2003a).
Identification and characterization of a G protein-coupled receptor for the
neuropeptide proctolin in Drosophila melanogaster. Proc. Natl.
Acad. Sci. USA 100,6198
-6203.
Johnson, E. C., Bohn, L. M., Barak, L. S., Birse, R. T., Nassel,
D. R., Caron, M. G. and Taghert, P. H. (2003b).
Identification of Drosophila neuropeptide receptors by G
protein-coupled receptors-beta-arrestin2 interactions. J. Biol.
Chem. 278,52172
-52178.
Johnson, E. C., Bohn, L. M. and Taghert, P. H.
(2004). Drosophila CG8422 encodes a functional diuretic
hormone receptor. J. Exp. Biol.
207,743
-748.
Kean, L., Cazenave, W., Costes, L., Broderick, K. E., Graham, S., Pollock, V. P., Davies, S. A., Veenstra, J. A. and Dow, J. A. (2002). Two nitridergic peptides are encoded by the gene capability in Drosophila melanogaster. Am. J. Physiol. 282,R1297 -R1307.
Kim, Y. J., Spalovska-Valachova, I., Cho, K. H., Zitnanova, I.,
Park, Y., Adams, M. E. and Zitnan, D. (2004).
Corazonin receptor signaling in ecdysis initiation. Proc. Natl.
Acad. Sci. USA 101,6704
-6709.
Kovacs, A., Biro, E., Szeleczky, I. and Telegdy, G. (1995). Role of endogenous CRF in the mediation of neuroendocrine and behavioral responses to calcitonin gene-related peptide in rats. Neuroendocrinology 62,418 -424.[Medline]
Kuwasako, K., Shimekake, Y., Masuda, M., Nakahara, K., Yoshida,
T., Kitaura, M., Kitamura, K., Eto, T. and Sakata, T.
(2000). Visualization of the calcitonin receptor-like receptor
and its receptor activity-modifying proteins during internalization and
recycling. J. Biol. Chem.
275,29602
-29609.
Li, X. F., Bowe, J. E., Mitchell, J. C., Brain, S. D., Lightman,
S. L. and O'Byrne, K. T. (2004). Stress-induced
suppression of the gonadotropin-releasing hormone pulse generator in the
female rat: a novel neural action for calcitonin gene-related peptide.
Endocrinology 145,1556
-1663.
Ma, W., Chabot, J. G., Powell, K. J., Jhamandas, K., Dickerson, I. M. and Quirion, R. (2003). Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems. Neuroscience 120,677 -694.[CrossRef][Medline]
McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M. G. and Foord, S. M. (1998). RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393,333 -339.[CrossRef][Medline]
Oakley, R. H., Laporte, S. A., Holt, J. A., Caron, M. G. and
Barak, L. S. (2000). Differential affinities of visual
arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors
delineate two major classes of receptors. J. Biol.
Chem. 275,17201
-17210.
Oakley, R. H., Laporte, S. A., Holt, J. A., Barak, L. S. and
Caron, M. G. (2001). Molecular determinants underlying the
formation of stable intracellular G protein-coupled receptor-beta-arrestin
complexes after receptor endocytosis*. J. Biol.
Chem. 276,19452
-19460.
O'Donnell, M. J., Dow, J. A., Heusmann, G. R., Tublitz, N. J.
and Maddrell, S. H. (1996). Separate control of anion
and cation transport in Malpighian tubules of Drosophila
melanogaster. J. Exp. Biol.
199,1163
-1175.
Park, Y., Kim, Y. J. and Adams, M. E. (2002).
Identification of G protein-coupled receptors for Drosophila
PRXamide, CCAP, corazonin, and AKH supports a theory of ligand-receptor
coevolution. Proc. Natl. Acad. Sci. USA
99,11423
-11428.
Prado, M. A., Evans-Bain, B. and Dickerson, I. M. (2002). Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction. Biochem. Soc. Trans. 30,460 -464.[CrossRef][Medline]
Radford, J. C., Davies, S. A. and Dow, J. A.
(2002). Systematic G-protein-coupled receptor analysis in
Drosophila melanogaster identifies a leucokinin receptor with novel
roles. J. Biol. Chem.
277,38810
-38817.
Reagan, J. D. (1994). Expression cloning of an
insect diuretic hormone receptor. A member of the calcitonin/secretin receptor
family. J. Biol. Chem.
269, 9-12.
Riehle, M. A., Garczynski, S. F., Crim, J. W., Hill, C. A. and
Brown, M. R. (2002). Neuropeptides and peptide
hormones in Anopheles gambiae. Science
298,172
-175.
Roh, J., Chang, C. L., Bhalla, A., Klein, C. and Hsu, S. Y.
(2004). Intermedin is a calcitonin/calcitonin gene-related
peptide family peptide acting through the calcitonin receptor-like
receptor/receptor activity-modifying protein receptor complexes. J.
Biol. Chem. 279,7264
-7274.
Sozen, M. A., Armstrong, J. D., Yang, M., Kaiser, K. and Dow, J.
A. (1997). Functional domains are specified to single-cell
resolution in a Drosophila epithelium. Proc. Natl. Acad.
Sci. USA 94,5207
-5212.
Takei, Y., Inoue, K., Ogoshi, M., Kawahara, T., Bannai, H. and Miyano, S. (2004). Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator. FEBS Lett. 556,53 -58.[CrossRef][Medline]
Tawfik, A. I., Tanaka, S., de Loof, A., Schoofs, L., Baggerman,
G., Waelkens, E., Derua, R., Milner, Y., Yerushalmi, Y. and Pener, M.
P. (1999). Identification of the gregarization-associated
dark-pigmentotropin in locusts through an albino mutant. Proc.
Natl. Acad. Sci. USA 96,7083
-7087.
Tohgo, A., Choy, E. W., Gesty-Palmer, D., Pierce, K. L.,
Laporte, S., Oakley, R. H., Caron, M. G., Lefkowitz, R. J. and
Luttrell, L. M. (2003). The stability of the G
protein-coupled receptor-beta-arrestin interaction determines the mechanism
and functional consequence of ERK activation. J. Biol.
Chem. 278,6258
-6267.
Veenstra, J. A. (1989). Isolation and structure of corazonin, a cardioactive peptide from the American cockroach. FEBS Lett. 250,231 -234.[CrossRef][Medline]
Wang, J., Kean, L., Yang, J., Allan, A. K., Davies, S. A., Herzyk, P. and Dow, J. A. (2004). Function-informed transcriptome analysis of Drosophila renal tubule. Genome Biol. 5,R69 .[CrossRef][Medline]
Wise, S., Davis, N. T., Tyndale, E., Noveral, J., Folwell, M. G., Bedian, V., Emery, I. F. and Siwicki, K. K. (2002). Neuroanatomical studies of period gene expression in the hawkmoth, Manduca sexta. J. Comp. Neurol. 447,366 -380.[CrossRef][Medline]
Yamano, M. and Tohyama, M. (1994). Distribution of corticotropin-releasing factor and calcitonin gene-related peptide in the developing mouse cerebellum. Neurosci. Res. 19,387 -396.[CrossRef][Medline]
Related articles in JEB: