The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein.
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.
He
Lisheng
L
Department of Biochemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Zhang
Zhaojun
Z
Yu
Yan
Y
Ahmed
Sohail
S
Cheung
Nam Sang
NS
Qi
Robert Z
RZ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002154:Calpain / Q000378:metabolism; D002522:Chlorocebus aethiops; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding
D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D051360:Cyclin-Dependent Kinase 5; D002154:Calpain