Arginine methylation by PRMT2 controls the functions of the actin nucleator Cobl. Hou et al.

Published: 11 July 2018| Version 1 | DOI: 10.17632/j5cr8n5y74.1
Michael M. Kessels


examples of new original data - the file names refer to the respective figure panels in Hou et al Arginine methylation by PRMT2 controls the functions of the actin nucleator Cobl Wenya Hou1, Sabine Nemitz1, Simone Schopper2, Michael Lund Nielsen2, Michael Manfred Kessels1*, Britta Qualmann1* 1 Institute of Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, 07743 Jena, Germany 2 Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, DK-2200 Copenhagen N, Denmark Lead contact * Corresponding authors: M. M. Kessels & B. Qualmann Institut für Biochemie I, UKJ, Nonnenplan 2-4, D-07743 Jena, Germany E-mail: Summary The complex architecture of neuronal networks in the brain requires tight control of the actin cytoskeleton. The actin nucleator Cobl is critical for neuronal morphogenesis. Here we unveil that Cobl is controlled by arginine methylation. Coprecipitations, coimmunoprecipitations, cellular reconstitutions and in vitro reconstitutions demonstrated that Cobl associates with the protein arginine methyltransferase PRMT2 in an SH3 domain-dependent manner and that this promotes methylation of Cobl’s actin nucleating C terminal domain. Consistently, PRMT2 phenocopied Cobl functions in both gain- and loss-of-function studies, both PRMT2- and Cobl-promoted dendritogenesis relied on methylation and PRMT2 required functionality of its catalytic and its SH3 domain. Furthermore, Cobl-mediated dendritic arborization required PRMT2, complex formation with PRMT2 and PRMT2’s catalytic activity. Mechanistic studies unveiled that Cobl methylation is key for Cobl’s actin binding. Therefore, arginine methylation is a regulatory mechanism reaching beyond controlling nuclear processes. It also controls a major, cytosolic, cytoskeletal component shaping neuronal cells.



Natural Sciences, Neuroscience, Cell Biology