title: ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1.
abstract: The AAA-ATPase Vps4 is critical for function of the MVB sorting pathway, which in turn impacts cellular phenomena ranging from receptor downregulation to viral budding to cytokinesis. Vps4 dissociates ESCRTs from endosomal membranes during MVB sorting, but it is unclear how Vps4 ATPase activity is synchronized with ESCRT release. Vta1 potentiates Vps4 activity and interacts with ESCRT-III family members. We have investigated the impact of Vta1 and ESCRT-III family members on Vps4 ATPase activity. Two distinct mechanisms of Vps4 stimulation are described: Vps2 can directly stimulate Vps4 via its MIT domain, whereas Vps60 stimulates via Vta1. Moreover, Did2 can stimulate Vps4 by both mechanisms in distinct contexts. Recent structural determination of the ESCRT-III-binding region of Vta1 unexpectedly revealed a MIT-like region. These data support a model wherein a network of MIT and MIT-like domain interactions with ESCRT-III subunits contributes to the regulation of Vps4 activity during MVB sorting.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Ishara F
authors.initials: IF
authors.lastname: Azmi
authors.forename: Brian A
authors.initials: BA
authors.lastname: Davies
authors.forename: Junyu
authors.initials: J
authors.lastname: Xiao
authors.forename: Markus
authors.initials: M
authors.lastname: Babst
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
authors.forename: David J
authors.initials: DJ
authors.lastname: Katzmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D007700:Kinetics; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C507674:CHMP2A protein, human; C498543:CHMP3 protein, human; C481529:CHMP4A protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; C487285:VTA1 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases