The Rho-GEF PIX-1 directs assembly or stability of lateral attachment structures between muscle cells

• Type of Material: Article
• Authors: Jasmine C. Moody, Emory University; Hiroshi Qadota, Emory University; April R. Reedy, Emory University; C. Denise Okafor, Emory University; Niveda Shanmugan, Emory University; Yohei Matsunaga, Emory University; Courtney J. Christian, Emory University; Eric Ortlund, Emory University; Guy Benian, Emory University
• Language: English
• Date: 2020-10-06
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-020-18852-4
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 11
• Issue: 1
• Start Page: 5010
• End Page: 5010
• Grant/Funding Information: Most of the nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This study was supported in-part by a NSF-Graduate Research Fellowship (DGE 1444932) to J.C.M., a NIH grant (R01DK115213-01S) to C.D.O., and from a NIH grant (R01AR064307) to G.M.B.
• Keywords: Science & Technology - Other Topics; MOLECULAR-DYNAMICS; IDENTIFICATION; GTPASE; Science & Technology; PROTEIN; LOCALIZATION; GENETICS; Multidisciplinary Sciences; UNC-89; CAENORHABDITIS-ELEGANS; MUTATIONS; UNC-97/PINCH
• Research Categories: Physics, Molecular; Biology, Genetics

Abstract

PIX proteins are guanine nucleotide exchange factors (GEFs) that activate Rac and Cdc42, and are known to have numerous functions in various cell types. Here, we show that a PIX protein has an important function in muscle. From a genetic screen in C. elegans, we found that pix-1 is required for the assembly of integrin adhesion complexes (IACs) at borders between muscle cells, and is required for locomotion of the animal. A pix-1 null mutant has a reduced level of activated Rac in muscle. PIX-1 localizes to IACs at muscle cell boundaries, M-lines and dense bodies. Mutations in genes encoding proteins at known steps of the PIX signaling pathway show defects at muscle cell boundaries. A missense mutation in a highly conserved residue in the RacGEF domain results in normal levels of PIX-1 protein, but a reduced level of activated Rac in muscle, and abnormal IACs at muscle cell boundaries.