Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
In eukaryotes, the multivesicular body (MVB) sorting pathway plays an essential role in regulating cell surface protein composition, thereby impacting numerous cellular functions. Vps4, an ATPase associated with a variety of cellular activities, is required late in the MVB sorting reaction to dissociate the endosomal sorting complex required for transport (ESCRT), a requisite for proper function of this pathway. However, regulation of Vps4 function is not understood. We characterize Vta1 as a positive regulator of Vps4 both in vivo and in vitro. Vta1 promotes proper assembly of Vps4 and stimulates its ATPase activity through the conserved Vta1/SBP1/LIP5 region present in Vta1 homologues across evolution, including human SBP1 and Arabidopsis thaliana LIP5. These results suggest an evolutionarily conserved mechanism through which the disassembly of the ESCRT proteins, and thereby MVB sorting, is regulated by the Vta1/SBP1/LIP5 proteins.
Azmi
Ishara
I
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Davies
Brian
B
Dimaano
Christian
C
Payne
Johanna
J
Eckert
Debra
D
Babst
Markus
M
Katzmann
David J
DJ
D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology*
D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; C487285:VTA1 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases