title: Very-KIND, a KIND domain containing RasGEF, controls dendrite growth by linking Ras small GTPases and MAP2.
abstract: The regulation of cytoskeletal components in the dendritic shaft core is critical for dendrite elongation and branching. Here, we report that a brain-specific Ras guanine nucleotide exchange factor (RasGEF) carrying two kinase non-catalytic C-lobe domains (KINDs), very-KIND (v-KIND), regulates microtubule-associated protein 2 (MAP2). v-KIND is expressed in developing mouse brain, predominantly in the cerebellar granule cells. v-KIND not only activates Ras small GTPases via the C-terminal RasGEF domain, but also specifically binds to MAP2 via the second KIND domain (KIND2), leading to threonine phosphorylation of MAP2. v-KIND overexpression suppresses dendritic extension and branching of hippocampal neurons and cerebellar granule cells, whereas knockdown of endogenous v-KIND expression promotes dendrite growth. These findings suggest that v-KIND mediates a signaling pathway that links Ras and MAP2 to control dendrite growth.
authors.affiliation: Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Huang
authors.forename: Asako
authors.initials: A
authors.lastname: Furuya
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002384:Catalysis; D002531:Cerebellum / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014018:Tissue Distribution; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D020663:ras Guanine Nucleotide Exchange Factors; C511876:very-KIND protein, mouse