Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid

Leslie A. McCauliff, Annette Langan, Ran Li, Olga Ilnytska, Debosreeta Bose, Miriam Waghalter, Kimberly Lai, Peter C. Kahn, Judith Storch

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Unesterified cholesterol accumulation in the late endosomal/lysosomal (LE/LY) compartment is the cellular hallmark of Niemann-Pick C (NPC) disease, caused by defects in the genes encoding NPC1 or NPC2. We previously reported the dramatic stimulation of NPC2 cholesterol transport rates to and from model membranes by the LE/LY phospholipid lysobisphosphatidic acid (LBPA). It had been previously shown that enrichment of NPC1-deficient cells with LBPA results in cholesterol clearance. Here we demonstrate that LBPA enrichment in human NPC2-deficient cells, either directly or via its biosynthetic precursor phosphtidylglycerol (PG), is entirely ineffective, indicating an obligate functional interaction between NPC2 and LBPA in cholesterol trafficking. We further demonstrate that NPC2 interacts directly with LBPA and identify the NPC2 hydrophobic knob domain as the site of interaction. Together these studies reveal a heretofore unknown step of intracellular cholesterol trafficking which is critically dependent upon the interaction of LBPA with functional NPC2 protein.

Original languageEnglish (US)
StatePublished - Oct 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid'. Together they form a unique fingerprint.

Cite this