Cdk-mediated phosphorylation of the Kv beta 2 auxiliary subunit regulates Kv1 channel axonal targeting

Vacher, H; Yang, JW; Cerda O.; Autillo-Touati, A; Dargent, B; Trimmer, JS

Abstract

Kv1 channels are concentrated at specific sites in the axonal membrane, where they regulate neuronal excitability. Establishing these distributions requires regulated dissociation of Kv1 channels from the neuronal trafficking machinery and their subsequent insertion into the axonal membrane. We find that the auxiliary Kv. 2 subunit of Kv1 channels purified from brain is phosphorylated on serine residues 9 and 31, and that cyclin-dependent kinase (Cdk)-mediated phosphorylation at these sites negatively regulates the interaction of Kv beta 2 with the microtubule plus end-tracking protein EB1. Endogenous Cdks, EB1, and Kv. 2 phosphorylated at serine 31 are colocalized in the axons of cultured hippocampal neurons, with enrichment at the axon initial segment (AIS). Acute inhibition of Cdk activity leads to intracellular accumulation of EB1, Kv. 2, and Kv1 channel subunits within the AIS. These studies reveal a new regulatory mechanism for the targeting of Kv1 complexes to the axonal membrane through the reversible Cdk phosphorylation-dependent binding of Kv beta 2 to EB1.

Más información

Título según WOS: Cdk-mediated phosphorylation of the Kv beta 2 auxiliary subunit regulates Kv1 channel axonal targeting
Título de la Revista: JOURNAL OF CELL BIOLOGY
Volumen: 192
Número: 5
Editorial: ROCKEFELLER UNIV PRESS
Fecha de publicación: 2011
Página de inicio: 813
Página final: 824
Idioma: English
DOI:

10.1083/jcb.201007113

Notas: ISI