Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components of subcellular lipid transport.
Niemann-Pick C 1 (NPC1) is a large integral membrane glycoprotein that resides in late endosomes, whereas NPC2 is a small soluble protein found in the lumen of lysosomes. Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments, which results in lysosomal storage of a complex mixture of lipids, primarily cholesterol and glycosphingolipids. What are the biological functions of the NPC1 and NPC2 proteins? Here we review what is known about the intracellular itinerary of these two proteins as they facilitate lipid transport. We propose that the intracellular trafficking patterns of these proteins will provide clues about their function.
Liscum
Laura
L
Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. laura.liscum@tufts.edu
Sturley
Stephen L
SL
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000378:metabolism*; D021381:Protein Transport; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins