title: Function of the Drosophila receptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance.
abstract: The second messengers cAMP and cGMP modulate attraction and repulsion mediated by neuronal guidance cues. We find that the Drosophila receptor guanylyl cyclase Gyc76C genetically interacts with Semaphorin 1a (Sema-1a) and physically associates with the Sema-1a receptor plexin A (PlexA). PlexA regulates Gyc76C catalytic activity in vitro, and each distinct Gyc76C protein domain is crucial for regulating Gyc76C activity in vitro and motor axon guidance in vivo. The cytosolic protein dGIPC interacts with Gyc76C and facilitates Sema-1a-PlexA/Gyc76C-mediated motor axon guidance. These findings provide an in vivo link between semaphorin-mediated repulsive axon guidance and alteration of intracellular neuronal cGMP levels.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kayam
authors.initials: K
authors.lastname: Chak
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002384:Catalysis; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D039961:Semaphorins; C553161:kermit protein, Drosophila; C116483:plexA protein, Drosophila; C477531:semaphorin 1a, Drosophila; D006162:Guanylate Cyclase; C092949:Gyc76C protein, Drosophila; D006152:Cyclic GMP
keywords: Axon guidance; Gyc76C; Plexin A; Receptor guanylyl cyclase; Semaphorin-1a; cGMP; dGIPC