The scaffold protein JIP3 functions as a downstream effector of the small GTPase ARF6 to regulate neurite morphogenesis of cortical neurons.
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.
Suzuki
Atsushi
A
Department of Physiological Chemistry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Arikawa
Chihiro
C
Kuwahara
Yuji
Y
Itoh
Kouichi
K
Watanabe
Masatomo
M
Watanabe
Hiroshi
H
Suzuki
Teruhiko
T
Funakoshi
Yuji
Y
Hasegawa
Hiroshi
H
Kanaho
Yasunori
Y
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
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