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

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

Author information

1
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of Americ.
2
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
3
Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
4
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.

Abstract

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.

PMID:
24949636
PMCID:
PMC4065073
DOI:
10.1371/journal.pone.0100660
[Indexed for MEDLINE]
Free PMC Article

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