Disease relevance of SRGAP3

• Here, we report the isolation of a previously uncharacterized gene, MEGAP, which is disrupted and functionally inactivated by a translocation breakpoint in a patient who shares some characteristic clinical features, such as hypotonia and severe MR, with the 3p(-) syndrome [1].
• To investigate the effects of MEGAP on these cellular processes, we have established an inducible cell culture model consisting of a stably transfected neuroblastoma SHSY-5Y cell line that endogenously expresses MEGAP albeit at low levels [2].

Psychiatry related information on SRGAP3

• The WAVE-associated GTPase activating protein called WRP is implicated in human mental retardation, and WAVE-1 knock-out mice have altered behavior [3].

High impact information on SRGAP3

• MEGAP/srGAP3 mRNA is predominantly and highly expressed in fetal and adult brain, specifically in the neurons of the hippocampus and cortex, structures known to play a pivotal role in higher cognitive function, learning, and memory [1].
• We can show that the induced expression of MEGAP leads to the loss of filopodia and lamellipodia protrusions, whereas constitutively activated Rac1 and Cdc42 can rescue the formation of these structures [2].
• MEGAP expressing cells also showed impeded microtubule dynamics as demonstrated in the TC-7 3x-GFP epithelial kidney cells [2].
• MEGAP impedes cell migration via regulating actin and microtubule dynamics and focal complex formation [2].
• In contrast to the wild type, overexpression of MEGAP harbouring an artificially introduced missense mutation R542I within the functionally important GAP domain did not exert a visible effect on actin and microtubule cytoskeleton remodelling [2].

Biological context of SRGAP3

• By time-lapse microscopy, we show that induced MEGAP expression reduces cell migration by 3.8-fold and protrusion formation by 9-fold [2].

References