title: The scaffold protein JIP3 functions as a downstream effector of the small GTPase ARF6 to regulate neurite morphogenesis of cortical neurons.
abstract: The small GTPase ADP-ribosylation factor 6 (ARF6) plays crucial roles in a wide variety of cell functions. To better understand the molecular mechanisms of ARF6-mediated signaling and cellular functions, we sought new ARF6-binding proteins in the mouse brain. We identified the signaling scaffold protein JNK-interacting protein 3 (JIP3), which is exclusively expressed in neurons, as a downstream effector of ARF6. Overexpression of a unique dominant negative mutant of ARF6, which was unable to interact with JIP3, and knockdown of JIP3 in mouse cortical neurons stimulated the elongation and branching of neurites. These results provide evidence that ARF6/JIP3 signaling regulates neurite morphogenesis.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Chihiro
authors.initials: C
authors.lastname: Arikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Kouichi
authors.initials: K
authors.lastname: Itoh
authors.forename: Masatomo
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Funakoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kanaho
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000089982:ADP-Ribosylation Factor 6; D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; C468928:Spag9 protein, mouse; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse