Proteomics analysis of the non-muscle myosin heavy chain IIa-enriched actin-myosin complex reveals multiple functions within the podocyte

PLoS One. 2014 Jun 20;9(6):e100660. doi: 10.1371/journal.pone.0100660. eCollection 2014.


MYH9 encodes non-muscle myosin heavy chain IIA (NMMHCIIA), the predominant force-generating ATPase in non-muscle cells. Several lines of evidence implicate a role for MYH9 in podocytopathies. However, NMMHCIIA's function in podocytes remains unknown. To better understand this function, we performed immuno-precipitation followed by mass-spectrometry proteomics to identify proteins interacting with the NMMHCIIA-enriched actin-myosin complexes. Computational analyses revealed that these proteins belong to functional networks including regulators of cytoskeletal organization, metabolism and networks regulated by the HIV-1 gene nef. We further characterized the subcellular localization of NMMHCIIA within podocytes in vivo, and found it to be present within the podocyte major foot processes. Finally, we tested the effect of loss of MYH9 expression in podocytes in vitro, and found that it was necessary for cytoskeletal organization. Our results provide the first survey of NMMHCIIA-enriched actin-myosin-interacting proteins within the podocyte, demonstrating the important role of NMMHCIIA in organizing the elaborate cytoskeleton structure of podocytes. Our characterization of NMMHCIIA's functions goes beyond the podocyte, providing important insights into its general molecular role.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / biosynthesis
  • Actins / metabolism*
  • Animals
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Motor Proteins / biosynthesis
  • Molecular Motor Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Myosin Heavy Chains / biosynthesis
  • Myosin Heavy Chains / metabolism*
  • Podocytes / metabolism
  • Protein Interaction Maps
  • Proteomics*
  • nef Gene Products, Human Immunodeficiency Virus / metabolism


  • Actins
  • Cytoskeletal Proteins
  • MYH9 protein, human
  • Membrane Proteins
  • Molecular Motor Proteins
  • Multiprotein Complexes
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Myosin Heavy Chains