title: Proteomics analysis of the non-muscle myosin heavy chain IIa-enriched actin-myosin complex reveals multiple functions within the podocyte.
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.
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of Americ.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hays
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Clark
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tan
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of Americ.
authors.forename: Avelino
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of Americ.
authors.forename: Angela
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Jae W
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Nora
authors.initials: N
authors.lastname: Burdis
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Amol O
authors.initials: AO
authors.lastname: Bajaj
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of Americ.
authors.forename: John C
authors.initials: JC
authors.lastname: He
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Hyink
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Klotman
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D020409:Molecular Motor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C103814:MYH9 protein, human; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D046912:Multiprotein Complexes; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D018995:Myosin Heavy Chains