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.
Expression of plant immune genes is controlled by the opposing actions of ubiquitin ligases and deubiquitinases that modify the master coactivator NPR1, thereby regulating its intrinsic transcriptional activity.
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.
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.
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.
Nucleolar protein localization involves the phase separation within the nucleolar matrix via three types of multivalent features: acidic tracts, nucleic acid binding domains and arginine-rich low complexity sequences.
LAMP proteins, the major glycoproteins of the lysosome membrane, bind cholesterol directly and specifically, and interact with NPC1 and NPC2 proteins as part of the lysosomal cholesterol export process.