title: Dock7: a GEF for Rho-family GTPases and a novel myosin VI-binding partner in neuronal PC12 cells.
abstract: Myosin VI (MVI), the only known myosin that walks towards the minus end of actin filaments, is involved in several processes such as endocytosis, cell migration, and cytokinesis. It may act as a transporting motor or a protein engaged in actin cytoskeleton remodelling via its binding partners, interacting with its C-terminal globular tail domain. By means of pull-down technique and mass spectrometry, we identified Dock7 (dedicator of cytokinesis 7) as a potential novel MVI-binding partner in neurosecretory PC12 cells. Dock7, expressed mainly in neuronal cells, is a guanine nucleotide exchange factor (GEF) for small GTPases, Rac1 and Cdc42, which are the major regulators of actin cytoskeleton. MVI-Dock7 interaction was further confirmed by co-immunoprecipitation of endogenous MVI complexed with Dock7. In addition, MVI and Dock7 colocalized in interphase and dividing cells. We conclude that in PC12 cells MVI-Dock7 complexes may function at different cellular locations during the entire cell cycle. Of note, MVI and Dock7 colocalized in primary culture hippocampal neurons also, predominantly in the outgrowths. We hypothesize that this newly identified interaction between MVI and Dock7 may help explain a mechanism for MVI-dependent regulation of actin cytoskeleton organization.
authors.affiliation: Laboratory of Molecular Basis of Cell Motility, Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-093 Warsaw, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Majewski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sobczak
authors.forename: Serhiy
authors.initials: S
authors.lastname: Havrylov
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jóźwiak
authors.forename: Maria Jolanta
authors.initials: MJ
authors.lastname: Rędowicz
mesh_terms: D000818:Animals; D001665:Binding Sites; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D053719:Tandem Mass Spectrometry; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C089785:myosin VI; D018995:Myosin Heavy Chains; D020741:rho GTP-Binding Proteins