PMID- 10637304
OWN - NLM
STAT- MEDLINE
DCOM- 20000407
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 11
IP  - 1
DP  - 2000 Jan
TI  - ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs
      cholesterol trafficking.
PG  - 227-39
AB  - The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal
      trafficking that couples membrane association to its ATPase cycle. To investigate
      the function of mammalian VPS4 in endosomal trafficking, we have transiently
      expressed wild-type or ATPase-defective human VPS4 (hVPS4) in cultured cells.
      Wild-type hVPS4 was cytosolic, whereas a substantial fraction of hVPS4 that was
      unable to either bind or hydrolyze ATP was localized to membranes, including
      those of specifically induced vacuoles. Vacuoles were exclusively endocytic in
      origin, and subsets of enlarged vacuoles stained with markers for each stage of
      the endocytic pathway. Sorting of receptors from the early endosome to the
      recycling compartment or to the trans-Golgi network was not significantly
      affected, and no mutant hVPS4 associated with these compartments. However, many
      hVPS4-induced vacuoles were substantially enriched in cholesterol relative to the
      endosomal compartments of untransfected cells, indicating that expression of
      mutant hVPS4 gives rise to a kinetic block in postendosomal cholesterol sorting. 
      The phenotype described here is largely consistent with the defects in vacuolar
      sorting associated with class E vps mutants in yeast, and a role for mammalian
      VPS4 is discussed in this context.
FAU - Bishop, N
AU  - Bishop N
AD  - School of Biological Sciences, University of Manchester, Manchester M13 9PT,
      United Kingdom.
FAU - Woodman, P
AU  - Woodman P
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Fungal Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (VPS4 protein, S cerevisiae)
RN  - 0 (Vesicular Transport Proteins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
RN  - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
RN  - EC 3.6.4.6 (VPS4A protein, human)
RN  - EC 3.6.4.6 (Vps4b protein, mouse)
SB  - IM
MH  - ATPases Associated with Diverse Cellular Activities
MH  - Adenosine Triphosphatases/genetics/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cholesterol/*metabolism
MH  - Cricetinae
MH  - Endosomal Sorting Complexes Required for Transport
MH  - Endosomes/*metabolism
MH  - Fungal Proteins/genetics/metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Rats
MH  - Repressor Proteins/genetics/metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - Vacuolar Proton-Translocating ATPases
MH  - Vesicular Transport Proteins
PMC - PMC14770
EDAT- 2000/01/19 00:00
MHDA- 2000/01/19 00:01
CRDT- 2000/01/19 00:00
PHST- 2000/01/19 00:00 [pubmed]
PHST- 2000/01/19 00:01 [medline]
PHST- 2000/01/19 00:00 [entrez]
AID - 10.1091/mbc.11.1.227 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2000 Jan;11(1):227-39. doi: 10.1091/mbc.11.1.227.