[Abstract Title]. - Society for Neuroscience

Authors: *T. FURUICHI, J. HUANG, A. FURUYA, Y. SHINODA;
Lab. for Mol. Neurogenesis, RIKEN Brain Sci. Inst., Wako, Japan
Abstract: The kinase non-catalytic C-lobe domain (KIND) is a putative protein-protein
interaction module identified in three proteins; the actin-nucleation factor Spir, non-receptor-type
protein tyrosine phosphatase 13 (PTPN13), and the brain-specific Ras guanine nucleotide
exchange factor (RasGEF) very-KIND (v-KIND). However, the function of the KIND domain
has been unclear. v-KIND is unique in that it contains two tandemly-repeated KIND domains,
KIND1 and KIND2 (see Figure). We previously showed that v-KIND is colocalized with
microtubule-associated protein 2 (MAP2) in the dendrites of hippocampal neurons and cerebellar
granule cells, and is involved in dendrite growth and branching by regulating the activation of
Ras small GTPase, which probably leads to the threonine (Thr) phosphorylation of MAP2.
Overexpression of v-KIND suppresses dendritic extension and branching of hippocampal
neurons and cerebellar granule cells, whereas knockdown of endogenous v-KIND expression by
RNAi promotes dendrite growth. In this study, to understand the role of v-KIND-Ras-MAP2
signaling in microtubule-mediated dendrite growth, we analyzed the structural determinants and
functional properties of the v-KIND-MAP2 interaction. Among four KIND domains that we
tested, only the v-KIND KIND2 domain possesses MAP2 binding activity. Our study reveals the
modules involved in the interaction between v-KIND KIND2 domain and MAP2, which confers
the ability to localize v-KIND to dendrites where MAP2 is associated with microtubules. These
results indicate that the interaction of v-KIND with MAP2 via the KIND2 domain is essential for
the initial step of v-KIND-Ras-MAP2 signaling. (Figure: A model of the v-KIND-Ras-MAP2
signaling in dendrite growth)
Disclosures: T. Furuichi , None; J. Huang, None; A. Furuya, None; Y. Shinoda, None.