RGD Reference Report - P-Rex1 - a multidomain protein that regulates neurite differentiation.

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P-Rex1 - a multidomain protein that regulates neurite differentiation.
Authors:	Waters, JE Astle, MV Ooms, LM Balamatsias, D Gurung, R Mitchell, CA
Citation:	Waters JE, etal., J Cell Sci. 2008 Sep 1;121(Pt 17):2892-903. Epub 2008 Aug 12.
RGD ID:	2314615
Pubmed:	PMID:18697831 (View Abstract at PubMed)
DOI:	DOI:10.1242/jcs.030353 (Journal Full-text)
The Rac-GEF P-Rex1 promotes membrane ruffling and cell migration in response to Rac activation, but its role in neuritogenesis is unknown. Rac1 promotes neurite differentiation; Rac3, however, may play an opposing role. Here we report that in nerve growth factor (NGF)-differentiated rat PC12 cells, P-Rex1 localised to the distal tips of developing neurites and to the axonal shaft and growth cone of differentiating hippocampal neurons. P-Rex1 expression inhibited NGF-stimulated PC12 neurite differentiation and this was dependent on the Rac-GEF activity of P-Rex1. P-Rex1 inhibition of neurite outgrowth was rescued by low-dose cytochalasin D treatment, which prevents actin polymerisation. P-Rex1 activated Rac3 GTPase activity when coexpressed in PC12 cells. In the absence of NGF stimulation, targeted depletion of P-Rex1 in PC12 cells by RNA interference induced the spontaneous formation of beta-tubulin-enriched projections. Following NGF stimulation, enhanced neurite differentiation, with neurite hyper-elongation correlating with decreased F-actin at the growth cone, was demonstrated in P-Rex1 knockdown cells. Interestingly, P-Rex1-depleted PC12 cells exhibited reduced Rac3 and Rac1 GTPase activity. This study has identified P-Rex1 as a Rac3-GEF in neuronal cells that localises to, and regulates, actin cytoskeletal dynamics at the axonal growth cone to in turn regulate neurite differentiation.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Prex1	Rat	regulation of actin filament polymerization		IMP			RGD
Prex1	Rat	regulation of dendrite development		IMP			RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Prex1	Rat	dendritic shaft		IDA			RGD
Prex1	Rat	growth cone		IDA			RGD
Prex1	Rat	perinuclear region of cytoplasm		IDA			RGD

Objects Annotated

Genes (Rattus norvegicus)

Prex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1)

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P-Rex1 - a multidomain protein that regulates neurite differentiation.