PMID- 10479477
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20141120
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 68
IP  - 1
DP  - 1999 Sep
TI  - Niemann-Pick C1 is a late endosome-resident protein that transiently associates
      with lysosomes and the trans-Golgi network.
PG  - 1-13
AB  - Niemann-Pick type C (NPC) disease is a severe cell lipidosis characterized by the
      accumulation of unesterified cholesterol in the endosomal/lysosomal system.
      Recently the primary disease-causing gene, NPC1, was identified, but few clues
      regarding its potential function(s) could be derived from its predicted amino
      acid sequence. Therefore, efforts were directed at characterizing the subcellular
      location of the NPC1 protein. Initial studies with a FLAG-tagged NPC1 cDNA
      demonstrated that NPC1 is a glycoprotein that associates with the membranes of a 
      population of cytoplasmic vesicles. Immunofluorescence microscopy using anti-NPC1
      polyclonal antibodies confirmed this analysis. Double-label immunofluorescence
      microscopy and subcellular fractionation studies indicated that NPC1 associates
      predominantly with late endosomes (Rab9 GTPase-positive vesicles) and, to a
      lesser extent, with lysosomes and the trans-Golgi network. When cholesterol
      egress from lysosomes was blocked by treatment of cells with U18666A, the NPC1
      location shifted from late endosomes to the trans-Golgi network and lysosomes.
      Subcellular fractionation of liver homogenates from U18666A-treated mice
      confirmed these observations. These data suggest that U18666A may inhibit the
      retrograde transport of NPC1 from lysosomes to late endosomes for subsequent
      transfer to the trans-Golgi network.
CI  - Copyright 1999 Academic Press.
FAU - Higgins, M E
AU  - Higgins ME
AD  - Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 
      10029, USA.
FAU - Davies, J P
AU  - Davies JP
FAU - Chen, F W
AU  - Chen FW
FAU - Ioannou, Y A
AU  - Ioannou YA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Androstenes)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NPC1 protein, human)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 3039-71-2 (3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one)
RN  - 98849-88-8 (FLAG peptide)
SB  - IM
MH  - Androstenes/pharmacology
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology
MH  - Biological Transport/drug effects
MH  - COS Cells
MH  - *Carrier Proteins
MH  - Cell Line
MH  - Endosomes/*metabolism
MH  - Golgi Apparatus/*metabolism
MH  - Humans
MH  - Lysosomes/*metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Microscopy, Fluorescence
MH  - Oligopeptides
MH  - Peptides/genetics
MH  - Proteins/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1006/mgme.1999.2882 [doi]
AID - S1096-7192(99)92882-2 [pii]
PST - ppublish
SO  - Mol Genet Metab. 1999 Sep;68(1):1-13. doi: 10.1006/mgme.1999.2882.