SRGAP2

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SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) also known as formin-binding protein 2 (FNBP2) is a protein that in humans is encoded by the SRGAP2 gene.[1][2]

SRGAP2 is involved in neuronal migration and neuronal differentiation.[3] SRGAP2 also plays a critical role in synaptic development,[4] brain mass and the number of cortical neurons.[5]

SRGAP2C slows maturation of some neurons and increases neuronal spine density.

Downregulation of srGAP2 inhibits cell-cell repulsion and enhances cell-cell contact duration.

Gene duplication

This gene is one of the 23 genes that are duplicated in humans but not in other primates.[6]

This protein in humans has been duplicated three times in the human genome in the past 3.4 million years: one duplication 3.4 million years ago (mya) called SRGAP2B, a second duplication 2.4 mya (called SRGAP2C), and one final duplication ~1 mya (SRGAP2D). The ancestral gene SRGAP2 is found in all mammals and the human copy has been renamed SRGAP2A. The 2.4 million year-old duplication (SRGAP2C) expresses a shortened version that 100% of humans possess.[7] This shortened version SRGAP2C inhibits the function of the ancestral copy SRGAP2A and (1) allows faster migration of neurons by interfering with filopodia production and (2) slows the rate of synaptic maturation and increases the density of synapses in the cerebral cortex.[4]

References

  1. Madura T, Yamashita T, Kubo T, Tsuji L, Hosokawa K, Tohyama M (April 2004). "Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection". Brain Research. Molecular Brain Research. 123 (1–2): 76–80. doi:10.1016/j.molbrainres.2004.01.002. PMID 15046868.
  2. Wong K, Ren XR, Huang YZ, Xie Y, Liu G, Saito H, Tang H, Wen L, Brady-Kalnay SM, Mei L, Wu JY, Xiong WC, Rao Y (October 2001). "Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway". Cell. 107 (2): 209–21. doi:10.1016/S0092-8674(01)00530-X. PMID 11672528.
  3. Guerrier S, Coutinho-Budd J, Sassa T, Gresset A, Jordan NV, Chen K, Jin WL, Frost A, Polleux F (September 2009). "The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis". Cell. 138 (5): 990–1004. doi:10.1016/j.cell.2009.06.047. PMC 2797480. PMID 19737524.
  4. 4.0 4.1 Charrier C, Joshi K, Coutinho-Budd J, Kim JE, Lambert N, de Marchena J, Jin WL, Vanderhaeghen P, Ghosh A, Sassa T, Polleux F (May 2012). "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation". Cell. 149 (4): 923–35. doi:10.1016/j.cell.2012.03.034. PMC 3357949. PMID 22559944.
  5. Tiwary, BK (2016). "Evolution of the SRGAP2 gene is linked to intelligence in mammals". Biomedicine Hub. Karger. 1 (1). doi:10.1159/000443947.
  6. Sudmant PH, Kitzman JO, Antonacci F, Alkan C, Malig M, Tsalenko A, Sampas N, Bruhn L, Shendure J, Eichler EE (October 2010). "Diversity of human copy number variation and multicopy genes". Science. 330 (6004): 641–6. doi:10.1126/science.1197005. PMC 3020103. PMID 21030649.
  7. Dennis MY, Nuttle X, Sudmant PH, Antonacci F, Graves TA, Nefedov M, Rosenfeld JA, Sajjadian S, Malig M, Kotkiewicz H, Curry CJ, Shafer S, Shaffer LG, de Jong PJ, Wilson RK, Eichler EE (May 2012). "Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication". Cell. 149 (4): 912–22. doi:10.1016/j.cell.2012.03.033. PMC 3365555. PMID 22559943. Lay summarysciencenews.org.

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