title: The axon guidance function of Rap1 small GTPase is independent of PlexA RasGAP activity in Drosophila.
abstract: Plexins (Plexs) comprise a large family of cell surface receptors for semaphorins (Semas) that function as evolutionarily conserved guidance molecules. GTPase activating protein (GAP) activity for Ras family small GTPases has been implicated in plexin signaling cascades through its RasGAP domain. However, little is known about how Ras family GTPases are controlled in vivo by plexin signaling. Here, we found that Drosophila Rap1, a member of the Ras family of GTPases, plays an important role controlling intersegmental nerve b motor axon guidance during neural development. Gain-of-function studies using dominant-negative and constitutively active forms of Rap1 indicate that Rap1 contributes to axonal growth and guidance. Genetic interaction analyses demonstrate that the Sema-1a/PlexA-mediated repulsive guidance function is regulated positively by Rap1. Furthermore, neuronal expression of mutant PlexA robustly restored defasciculation defects in PlexA null mutants when the catalytic arginine fingers of the PlexA RasGAP domain critical for GAP activity were disrupted. However, deleting the RasGAP domain abolished the ability of PlexA to rescue the PlexA guidance phenotypes. These findings suggest that PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases.
authors: Department of Molecular Biology, Chonbuk National University, Jeonju, Jeollabukdo 54896, Republic of Korea.
authors: Da-Som
authors: DS
authors: Yang
authors: Department of Molecular Biology, Chonbuk National University, Jeonju, Jeollabukdo 54896, Republic of Korea.
authors: Seyun
authors: S
authors: Roh
authors: Department of Molecular Biology, Chonbuk National University, Jeonju, Jeollabukdo 54896, Republic of Korea. Electronic address: sjeong4@jbnu.ac.kr.
authors: Sangyun
authors: S
authors: Jeong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000071437:Axon Guidance / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D017344:Genes, Insect; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C000607855:RAP1 protein, Drosophila; C491146:RasGAP1 protein, Drosophila; D011956:Receptors, Cell Surface; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C116483:plexA protein, Drosophila; D020703:ras GTPase-Activating Proteins; D020559:Monomeric GTP-Binding Proteins
keywords: Axon guidance; Plexin A; Rap1; Ras1; RasGAP; Semaphorin-1a