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SRGAP3  -  SLIT-ROBO Rho GTPase activating protein 3

Homo sapiens

Synonyms: ARHGAP14, KIAA0411, KIAA1156, MEGAP, Mental disorder-associated GAP, ...
 
 
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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

 

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

  1. The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe mental retardation. Endris, V., Wogatzky, B., Leimer, U., Bartsch, D., Zatyka, M., Latif, F., Maher, E.R., Tariverdian, G., Kirsch, S., Karch, D., Rappold, G.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. MEGAP impedes cell migration via regulating actin and microtubule dynamics and focal complex formation. Yang, Y., Marcello, M., Endris, V., Saffrich, R., Fischer, R., Trendelenburg, M.F., Sprengel, R., Rappold, G. Exp. Cell Res. (2006) [Pubmed]
  3. A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory. Soderling, S.H., Guire, E.S., Kaech, S., White, J., Zhang, F., Schutz, K., Langeberg, L.K., Banker, G., Raber, J., Scott, J.D. J. Neurosci. (2007) [Pubmed]
 
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