RGD Reference Report - Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons.

General

Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons.
Authors:	Galic, Milos Tsai, Feng-Chiao Collins, Sean R Matis, Maja Bandara, Samuel Meyer, Tobias
Citation:	Galic M, etal., Elife. 2014 Dec 15;3:e03116. doi: 10.7554/eLife.03116.
RGD ID:	14402441
Pubmed:	PMID:25498153 (View Abstract at PubMed)
PMCID:	PMC4381785 (View Article at PubMed Central)
DOI:	DOI:10.7554/eLife.03116 (Journal Full-text)
In the vertebrate central nervous system, exploratory filopodia transiently form on dendritic branches to sample the neuronal environment and initiate new trans-neuronal contacts. While much is known about the molecules that control filopodia extension and subsequent maturation into functional synapses, the mechanisms that regulate initiation of these dynamic, actin-rich structures have remained elusive. Here, we find that filopodia initiation is suppressed by recruitment of ArhGAP44 to actin-patches that seed filopodia. Recruitment is mediated by binding of a membrane curvature-sensing ArhGAP44 N-BAR domain to plasma membrane sections that were deformed inward by acto-myosin mediated contractile forces. A GAP domain in ArhGAP44 triggers local Rac-GTP hydrolysis, thus reducing actin polymerization required for filopodia formation. Additionally, ArhGAP44 expression increases during neuronal development, concurrent with a decrease in the rate of filopodia formation. Together, our data reveals a local auto-regulatory mechanism that limits initiation of filopodia via protein recruitment to nanoscale membrane deformations.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
negative regulation of filopodium assembly	involved_in	IDA		14402441	PMID:25498153	UniProt
negative regulation of filopodium assembly		IMP		14402441		RGD

Cellular Component

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
dendrite	located_in	IDA		14402441	PMID:25498153	UniProt

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
GTPase activator activity	enables	IDA		14402441	PMID:25498153	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Arhgap44 (Rho GTPase activating protein 44)

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Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons.