The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells

Abstract

During peripheral nervous system development, Schwann cells undergo Rac1-dependent cytoskeletal reorganization as they insert cytoplasmic extensions into axon bundles to sort and myelinate individual axons. However, our understanding of the direct effectors targeted by Rac1 is limited. Here, we demonstrate that striatin-3 and MOB4 are Rac1 interactors. We show that Schwann-cell-specific ablation of striatin-3 causes defects in lamellipodia formation, and conditional Schwann cell knockout for striatins presents a severe delay in radial sorting. Finally, we demonstrate that deletion of Rac1 or striatin-1/3 in Schwann cells causes defects in the activation of Hippo pathway effectors YAP and TAZ and the expression of genes co-regulated by YAP and TAZ, such as extracellular matrix receptors. In summary, our results indicate that striatin-3 is a Rac1 interactor and that striatins are required for peripheral nervous system development and reveal a role for Rac1 in the regulation of the Hippo pathway in Schwann cells.

Keywords: CP: Metabolism; CP: Stem cell research; RAC1; STRIPAK; Schwann cells; YAP/TAZ; radial sorting.