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The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein
journal contribution
posted on 2023-05-17, 11:53 authored by He, LS, Zhang, ZJ, Yu, Y, Ahmed, S, Cheung, NS, Qi, RZThe 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.
History
Publication title
Cellular and Molecular Life SciencesVolume
68Issue
6Pagination
1633-1643ISSN
1420-682XDepartment/School
Menzies Institute for Medical ResearchPublisher
Birkhauser Verlag AgPlace of publication
Viadukstrasse 40-44, Po Box 133, Basel, Switzerland, Ch-4010Rights statement
Copyright 2011 Springer Basel AGRepository Status
- Restricted