Department of Human Molecular Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Mech Dev. 2013 Jun-Aug;130(6-8):391-5. doi: 10.1016/j.mod.2012.10.005. Epub 2012 Nov 2.
The Slit-Robo GTPase activating protein 3 (srGAP3) dynamically regulates cytoskeletal reorganisation through inhibition of the Rho GTPase Rac1 and interaction with actin remodelling proteins. SrGAP3-mediated reorganisation of the actin cytoskeleton is crucial for the normal development of dendritic spines and loss of srGAP3 leads to abnormal synaptic activity and impaired cognitive behaviours in mice, which is reminiscent of an association between disrupted srGAP3 and intellectual disability in humans. Additionally, srGAP3 has been implicated to act downstream of Slit-Robo signalling in commissural axons of the spinal cord. Thus, srGAP3-mediated cytoskeletal reorganisation has an important influence on a variety of neurodevelopmental processes, which may be required for normal cognitive function.
Slit-Robo GTPase 激活蛋白 3（srGAP3）通过抑制 Rho GTPase Rac1 并与肌动蛋白重塑蛋白相互作用，动态调节细胞骨架重组。srGAP3 介导的肌动蛋白细胞骨架重组对于树突棘的正常发育至关重要，srGAP3 的缺失导致小鼠异常的突触活动和认知行为受损，这使人联想到 srGAP3 与人类智力障碍之间的关联。此外，srGAP3 已被牵连在脊髓的连合轴突中的 Slit-Robo 信号下游发挥作用。因此，srGAP3 介导的细胞骨架重组对多种神经发育过程有重要影响，这可能是正常认知功能所必需的。
