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

Takashi Nishimura, Tomoya Yamaguchi, Akinori Tokunaga, Akitoshi Hara, Tomonari Hamaguchi, Katsuhiro Kato, Akihiro Iwamatsu, Hideyuki Okano, Kozo Kaibuchi

Research output: Contribution to journalArticle

84 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1273-1285
Number of pages13
JournalMolecular Biology of the Cell
Volume17
Issue number3
DOIs
Publication statusPublished - 2006 Mar

Fingerprint

Guanine Nucleotide Exchange Factors
Dendritic Spines
EphB2 Receptors
Endocytosis
Ephrin-B1
Spine
Neurons
Clathrin
Neurogenesis
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Morphogenesis
Nervous System
intersectin 1
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Nishimura, T., Yamaguchi, T., Tokunaga, A., Hara, A., Hamaguchi, T., Kato, K., ... Kaibuchi, K. (2006). Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Molecular Biology of the Cell, 17(3), 1273-1285. https://doi.org/10.1091/mbc.E05-07-0700

Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. / Nishimura, Takashi; Yamaguchi, Tomoya; Tokunaga, Akinori; Hara, Akitoshi; Hamaguchi, Tomonari; Kato, Katsuhiro; Iwamatsu, Akihiro; Okano, Hideyuki; Kaibuchi, Kozo.

In: Molecular Biology of the Cell, Vol. 17, No. 3, 03.2006, p. 1273-1285.

Research output: Contribution to journalArticle

Nishimura, T, Yamaguchi, T, Tokunaga, A, Hara, A, Hamaguchi, T, Kato, K, Iwamatsu, A, Okano, H & Kaibuchi, K 2006, 'Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2', Molecular Biology of the Cell, vol. 17, no. 3, pp. 1273-1285. https://doi.org/10.1091/mbc.E05-07-0700
Nishimura T, Yamaguchi T, Tokunaga A, Hara A, Hamaguchi T, Kato K et al. Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Molecular Biology of the Cell. 2006 Mar;17(3):1273-1285. https://doi.org/10.1091/mbc.E05-07-0700
Nishimura, Takashi ; Yamaguchi, Tomoya ; Tokunaga, Akinori ; Hara, Akitoshi ; Hamaguchi, Tomonari ; Kato, Katsuhiro ; Iwamatsu, Akihiro ; Okano, Hideyuki ; Kaibuchi, Kozo. / Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. In: Molecular Biology of the Cell. 2006 ; Vol. 17, No. 3. pp. 1273-1285.
@article{963b5fa61ec340aeb71c4ad1f4f7de09,
title = "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.",
author = "Takashi Nishimura and Tomoya Yamaguchi and Akinori Tokunaga and Akitoshi Hara and Tomonari Hamaguchi and Katsuhiro Kato and Akihiro Iwamatsu and Hideyuki Okano and Kozo Kaibuchi",
year = "2006",
month = "3",
doi = "10.1091/mbc.E05-07-0700",
language = "English",
volume = "17",
pages = "1273--1285",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "3",

}

TY - JOUR

T1 - Role of Numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2

AU - Nishimura, Takashi

AU - Yamaguchi, Tomoya

AU - Tokunaga, Akinori

AU - Hara, Akitoshi

AU - Hamaguchi, Tomonari

AU - Kato, Katsuhiro

AU - Iwamatsu, Akihiro

AU - Okano, Hideyuki

AU - Kaibuchi, Kozo

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33644858848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644858848&partnerID=8YFLogxK

U2 - 10.1091/mbc.E05-07-0700

DO - 10.1091/mbc.E05-07-0700

M3 - Article

C2 - 16394100

AN - SCOPUS:33644858848

VL - 17

SP - 1273

EP - 1285

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 3

ER -