Sterol kinetics and cell-based assays reveal a heretofore unknown step in cholesterol trafficking through the endolysosomal compartment, involving a direct functional interaction between NPC2 and lysosbisphosphatidic acid.
Fibroblast growth factor induces dephosphorylation and inactivation of the NPR2 guanylyl cyclase, thus decreasing cyclic GMP production in growth plate chondrocytes and contributing to FGF-dependent decreases in bone growth.
A structural analysis of the transcription regulator Mot1 in complex with promoter DNA and the proteins TBP and NC2 provides a first structural framework for how a Swi2/Snf2 type remodeler interacts with a histone fold protein:DNA complex.
The N-terminal domain of one NPC1 molecule can transfer its cholesterol to another NPC1 molecule lacking the N-terminal domain, suggesting that NPC1 forms multimers that transport cholesterol out of lysosomes.
A nanomolar inhibitor of cholesterol transport out of endosomes/lysosomes can be crosslinked to the “sterol-sensing domain” of NPC1, which implicates this domain in the transmembrane transport of cholesterol.
Molecular analysis of cholesterol transport by NPC1 and NPC1L1 proteins reveals that cholesterol likely moves through these transporters, and ezetimibe blocks NPC1L1 by binding at the interface between multiple domains.