Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2.

Abstract:

:Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling. Recent studies have revealed that Numb functions in clathrin-dependent endocytosis by binding to the AP-2 complex. Numb is also expressed in postmitotic neurons and plays a role in axonal growth. However, the functions of Numb in later stages of neuronal development remain unknown. Here, we report that Numb specifically localizes to dendritic spines in cultured hippocampal neurons and is implicated in dendritic spine morphogenesis, partially through the direct interaction with intersectin, a Cdc42 guanine nucleotide exchange factor (GEF). Intersectin functions as a multidomain adaptor for proteins involved in endocytosis and cytoskeletal regulation. Numb enhanced the GEF activity of intersectin toward Cdc42 in vivo. Expression of Numb or intersectin caused the elongation of spine neck, whereas knockdown of Numb and Numb-like decreased the protrusion density and its length. Furthermore, Numb formed a complex with EphB2 receptor-type tyrosine kinase and NMDA-type glutamate receptors. Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation. These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2.

journal_name

Mol Biol Cell

authors

Nishimura T,Yamaguchi T,Tokunaga A,Hara A,Hamaguchi T,Kato K,Iwamatsu A,Okano H,Kaibuchi K

doi

10.1091/mbc.e05-07-0700

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1273-85

issue

3

eissn

1059-1524

issn

1939-4586

pii

E05-07-0700

journal_volume

17

pub_type

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