Arginine Methylation by PRMT2 Controls the Functions of the Actin Nucleator Cobl

Publication date: 23 April 2018
Source:Developmental Cell, Volume 45, Issue 2
Author(s): Wenya Hou, Sabine Nemitz, Simone Schopper, Michael Lund Nielsen, Michael Manfred Kessels, Britta Qualmann
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 reveal 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 a Src Homology 3 (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. PRMT2 effects require both its catalytic domain and SH3 domain. Cobl-mediated dendritic arborization required PRMT2, complex formation with PRMT2, and PRMT2's catalytic activity. Mechanistic studies reveal that Cobl methylation is key for Cobl 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.

Graphical abstract

Teaser

Hou et al. demonstrate that early morphogenesis of neurons is dependent on arginine methylation. The authors identify the enzyme arginine methyltransferase PRMT2 as key regulator of the actin nucleator Cobl. PRMT2 methylates Cobl and promotes G-actin binding, thereby modulating Cobl's activity in dendritic arborization.


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