Niemann-Pick type C mutations cause lipid traffic jam.
The Niemann-Pick C protein (NPC1) is required for cholesterol transport from late endosomes and lysosomes to other cellular membranes. Mutations in NPC1 cause lysosomal lipid storage and progressive neurological degeneration. Cloning of the NPC1 gene has given us tools with which to investigate the function of this putative cholesterol transporter. Here, we discuss recent studies indicating that NPC1 is not a cholesterol-specific transport molecule. Instead, NPC1 appears to be required for the vesicular shuttling of both lipids and fluid-phase constituents from multivesicular late endosomes to destinations such as the trans-Golgi network.
Liscum
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Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. lliscum@opal.tufts.edu
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D016466:CHO Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013107:Sphingolipids / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*
D002352:Carrier Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D013107:Sphingolipids; D002784:Cholesterol