Steven R, Kubiseski T J, Zheng H, Kulkarni S, Mancillas J, Ruiz Morales A, Hogue C W, Pawson T, Culotti J
Samuel Lunenfeld Research Institute of Mt. Sinai Hospital, Toronto, Ontario, Canada.
Cell. 1998 Mar 20;92(6):785-95. doi: 10.1016/s0092-8674(00)81406-3.
unc-73 is required for cell migrations and axon guidance in C. elegans and encodes overlapping isoforms of 283 and 189 kDa that are closely related to the vertebrate Trio and Kalirin proteins, respectively. UNC-73A contains, in order, eight spectrin-like repeats, a Dbl/Pleckstrin homology (DH/PH) element, an SH3-like domain, a second DH/PH element, an immunoglobulin domain, and a fibronectin type III domain. UNC-73B terminates just downstream of the SH3-like domain. The first DH/PH element specifically activates the Rac GTPase in vitro and stimulates actin polymerization when expressed in Rat2 cells. Both functions are eliminated by introducing the S1216F mutation of unc-73(rh40) into this DH domain. Our results suggest that UNC-73 acts cell autonomously in a protein complex to regulate actin dynamics during cell and growth cone migrations.
unc-73基因对于秀丽隐杆线虫的细胞迁移和轴突导向是必需的，它编码283 kDa和189 kDa的重叠异构体，分别与脊椎动物的Trio和Kalirin蛋白密切相关。UNC-73A依次包含八个血影蛋白样重复序列、一个Dbl/普列克底物蛋白同源（DH/PH）元件、一个类SH3结构域、第二个DH/PH元件、一个免疫球蛋白结构域和一个纤连蛋白III型结构域。UNC-73B在类SH3结构域下游终止。第一个DH/PH元件在体外特异性激活Rac GTP酶，并在Rat2细胞中表达时刺激肌动蛋白聚合。通过将unc-73(rh40)的S1216F突变引入该DH结构域，这两种功能均被消除。我们的结果表明，UNC-73在蛋白质复合物中以细胞自主方式发挥作用，在细胞和生长锥迁移过程中调节肌动蛋白动力学。
