MEXT-JSPS KAKENHI, AMED-CREST

Countries/Regions
United States of America
Category
Research
Academic Field
Medicine
Related goals of SDGs
3 Good health and well-being17 Partnerships for the goals
Keyword phosphorylation, protein kinase, inhibitor, axon growth, synaptogenesis

Information on Niigata University

Name of the professor/researcher Michihiro Igarashi
Position/Faculty Professor, Gaduate School of Medical and Dental Sciences, and School of Medicine

Information on the Counterpart

Countries/Regions USA
Faculty/Institution Miami U, Miller Sch Med

Detailed Information/Report on Activities

Protein kinases are responsible for protein phosphorylation and are involved in important signal transduction pathways; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered cyclin G-associated kinase (GAK) as a candidate regulator of neurite outgrowth and synaptogenesis by examining the effects of the selective GAK inhibitor SGC-GAK-1. SGC-GAK-1 treatment of cultured neurons reduced neurite length and decreased synapse number and phosphorylation of neurofilament 200-kDa subunits relative to the control. In addition, the related kinase inhibitor erlotinib, which has distinct specificity and potency from SGC-GAK-1, had no effect on neurite growth, unlike SGC-GAK-1. These results suggest that GAK may be physiologically involved in normal neuronal development, and that decreased GAK function and the resultant impaired neurite outgrowth and synaptogenesis may be related to neurodevelopmental disorders.