Vps4 regulates a subset of protein interactions at the multivesicular endosome

Vajjhala, P. R., Catchpoole, E., Nguyen, C. H., Kistler, C. and Munn, A. L. (2007) Vps4 regulates a subset of protein interactions at the multivesicular endosome. FEBS Journal, 274 8: 1894-1907. doi:10.1111/j.1742-4658.2007.05736.x

Author Vajjhala, P. R.
Catchpoole, E.
Nguyen, C. H.
Kistler, C.
Munn, A. L.
Title Vps4 regulates a subset of protein interactions at the multivesicular endosome
Journal name FEBS Journal   Check publisher's open access policy
ISSN 1742-464X
Publication date 2007
Sub-type Article (original research)
DOI 10.1111/j.1742-4658.2007.05736.x
Volume 274
Issue 8
Start page 1894
End page 1907
Total pages 14
Place of publication United Kingdom
Publisher Wiley-Blackwell
Collection year 2008
Language eng
Subject C1
270199 Biochemistry and Cell Biology not elsewhere classified
730101 Infectious diseases
Abstract During endocytic transport, specific integral membrane proteins are sorted into intraluminal vesicles that bud from the limiting membrane of the endosome. This process, known as multivesicular body (MVB) sorting, is important for several important biological processes. Moreover, components of the MVB sorting machinery are implicated in virus budding. During MVB sorting, a cargo protein recruits components of the MVB sorting machinery from cytoplasmic pools and these sequentially assemble on the endosome. Disassembly of these proteins and recycling into the cytoplasm is critical for MVB sorting. Vacuolar protein sorting 4 (Vps4) is an AAA (ATPase associated with a variety of cellular activities) ATPase which has been proposed to play a critical role in disassembly of the MVB sorting machinery. However, the mechanism by which it disassembles the complex is not clear. Vps4 contains an N-terminal microtubule interacting and trafficking (MIT) domain, which has previously been shown to be required for recruitment to endosomes, and a single AAA ATPase domain, the activity of which is required for Vps4 function. In this study we have systematically characterized the interaction of Vps4 with other components of the MVB sorting machinery. We demonstrate that Vps4 interacts directly with Vps2 and Bro1. We also show that a subset of Vps4 interactions is regulated by ATP hydrolysis, and one interaction is regulated by ATP binding. Finally, we show that most proteins interact with the Vps4 MIT domain. Our studies indicate that the MIT domain has a dual role in substrate binding and recruitment to endosomes and indicate that Vps4 disassembles the MVB sorting machinery by direct effects on multiple proteins.
Keyword Biochemistry & Molecular Biology
macromolecular disassembly
membrane traffic
Prevacuolar Compartment
Membrane Association
Internalization Step
Escrt Complexes
Mit Domain
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Mon, 18 Feb 2008, 16:48:30 EST