Very-KIND, a KIND domain containing RasGEF, controls dendrite growth by linking Ras small GTPases and MAP2

J Cell Biol. 2007 Nov 5;179(3):539-52. doi: 10.1083/jcb.200702036.

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.

MeSH terms

  • Animals
  • Brain / metabolism
  • Catalysis
  • Cerebellum / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / physiology*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Microtubules / metabolism
  • Models, Biological
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction
  • Tissue Distribution
  • ras Guanine Nucleotide Exchange Factors / metabolism*

Substances

  • Guanine Nucleotide Exchange Factors
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Nerve Tissue Proteins
  • ras Guanine Nucleotide Exchange Factors
  • very-KIND protein, mouse