The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein
The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein
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DOI：
10.1007/s00018-010-0562-9
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发表时间：
2011-05-01
影响因子：
8
通讯作者：
Qi, Robert Z.
中科院分区：
文献类型：
--
作者：
He, Lisheng;Zhang, Zhaojun;Qi, Robert Z.
神经元Cdk5激活因子p35参与多种神经元活动，包括细胞骨架组织。我们在这里表明p35直接与丝状肌动蛋白（f -肌动蛋白）相互作用，但不与单体肌动蛋白（g -肌动蛋白）相互作用。通过结合，p35诱导肌动蛋白束的形成，并稳定f -肌动蛋白，防止稀释引起的解聚。P35形成分子间自结合，表明P35通过分子间自结合将肌动蛋白丝交联成束。p35二聚化和与f -肌动蛋白的结合发生在n端区域，而这在calpain-cleaved product p25中是不存在的，这表明p35的这种特性在神经毒性条件下被截断而丧失。利用Cdk5磷酸化的p35和突变方法，我们证明p35的磷酸化促进了它的同二聚化和p35诱导的f -肌动蛋白束的形成。此外，磷酸化调节p35在微管和肌动蛋白细胞骨架中的分布。总之，这些观察结果定义了p35在细胞骨架调节中的新功能。
The neuronal Cdk5 activator p35 is involved in a multitude of neuronal activities, including cytoskeletal organization. We show here that p35 directly interacts with filamentous actin (F-actin) but not with monomeric actin (G-actin). Through binding, p35 induces the formation of actin bundles and stabilizes F-actin against dilution-induced depolymerization. p35 forms intermolecular self-associations, suggesting that p35 cross-links actin filaments into bundles via its intermolecular self-association. p35 dimerization and association with F-actin occur at the N-terminal region that is absent in the calpain-cleaved product p25, indicating that such p35 properties are lost by its truncation induced under neurotoxic conditions. Using p35 phosphorylated by Cdk5 and a mutational approach, we demonstrate that the phosphorylation of p35 promotes its homodimerization and p35-induced formation of F-actin bundles. In addition, the phosphorylation regulates p35 distribution to microtubule and actin cytoskeletons. Together, these observations define a novel function for p35 in cytoskeletal regulation.