Research ArticleDevelopmental Neurobiology

Distinct Cytoplasmic Domains in Plexin-A4 Mediate Diverse Responses to Semaphorin 3A in Developing Mammalian Neurons

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Science Signaling  11 Mar 2014:
Vol. 7, Issue 316, pp. ra24
DOI: 10.1126/scisignal.2004734

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  • Separating the C1 and C2 domains of Plexin
    • Hua Chen, Postdoc, University of Texas Southwestern

    It has been known that the intracellular domain of Plexin shares sequence similarity to RasGAP (Ras GTPase activating protein). Consistent with this notion, the crystal structures of the intracellular domains of Plexins A3 and B1 clearly showed that the C1 and C2 regions form a GAP domain [PNAS 106, 15610-15615 (2009); JBC, 284, 35962-35972 (2009)]. The C1 and C2 regions interact with each other to form the GAP domain although they are separated by the RBD (Rho GTPase-binding domain). So C1 and C2 form an integrated domain in the 3-D structure. A recent paper published in PNAS indicated GAP activity is important for plexin function in developmental process using GAP activity-dead knock-in mice [PNAS 111, 2194-2199 (2014)].
    In my opinion, we cannot separate the C1 and C2 domains of plexin to study its biological function.

    Competing Interests: None declared.

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