RGD Reference Report - Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. - Rat Genome Database

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

Authors: Nishimura, T  Yamaguchi, T  Tokunaga, A  Hara, A  Hamaguchi, T  Kato, K  Iwamatsu, A  Okano, H  Kaibuchi, K 
Citation: Nishimura T, etal., Mol Biol Cell. 2006 Mar;17(3):1273-85. Epub 2006 Jan 4.
RGD ID: 2302413
Pubmed: PMID:16394100   (View Abstract at PubMed)
PMCID: PMC1382316   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E05-07-0700   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendritic spine located_inIDA 2302413; 2302413MMO:0000686RGD 
glutamatergic synapse is_active_inIDA 2302413; 2302413PMID:16394100SynGO 
glutamatergic synapse is_active_inIMP 2302413; 2302413PMID:16394100SynGO 
postsynaptic density is_active_inIDA 2302413PMID:16394100SynGO 
postsynaptic density is_active_inIMP 2302413PMID:16394100SynGO 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPINumb (Rattus norvegicus)2302413 RGD 
protein binding  IPIDpysl2 (Rattus norvegicus)2302413 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dpysl2  (dihydropyrimidinase-like 2)
Ephb2  (Eph receptor B2)
Numb  (NUMB, endocytic adaptor protein)
Numbl  (NUMB-like, endocytic adaptor protein)


Additional Information