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

Nat Commun. 2020 Oct 6;11(1):5010. doi: 10.1038/s41467-020-18852-4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation
  • Locomotion
  • Molecular Dynamics Simulation
  • Muscle Cells / physiology*
  • Muscles / cytology*
  • Mutation
  • Protein Domains
  • Rho Guanine Nucleotide Exchange Factors / chemistry
  • Sarcomeres / physiology
  • rac GTP-Binding Proteins / metabolism


  • ARHGEF7 protein, human
  • CED-10 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • PIX-1 protein, C elegans
  • Rho Guanine Nucleotide Exchange Factors
  • rac GTP-Binding Proteins