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.
Department of Biochemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Lisheng
L
He
Zhaojun
Z
Zhang
Yan
Y
Yu
Sohail
S
Ahmed
Nam Sang
NS
Cheung
Robert Z
RZ
Qi
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