Biology subjects

Anees, P.

Publications and source records attributed to Anees, P..

2 recordsLinked to original sources

bioRxiv2023

TMEM165 acts as a proton-activated Ca2+ importer in lysosomes

Lysosomal calcium (Ca2+) release is critical to cell signaling and is mediated by well-known lysosomal Ca2+ channels. Yet, how lysosomes refill their Ca2+ remains hitherto undescribed. Here, from an RNAi screen, we identify an evolutionarily conserved gene, lci-1, that facilitates lysosomal Ca2+ entry in C. elegans and in mammalian cells. Its human homolog TMEM165, previously designated as a Golgi-resident Ca2+/H+ exchanger (CAX), has a minor lysosomal population of unknown function. Using genetics, lysosomal Ca2+ imaging and electrophysiology, we show that TMEM165 acts as a proton-activated, lysosomal Ca2+ importer in lysosomes. Defects in lysosomal Ca2+ channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca2+ importers may provide new avenues to explore the physiology of Ca2+ channels.

cell biology↗

bioRxiv2023

Passive endocytosis in protocells enables nutrient transport bypassing permeability limits

Semipermeable membranes are a key feature of all living organisms. While specialized membrane transporters in cells can import otherwise impermeable nutrients, the earliest cells would have lacked a mechanism to import nutrients rapidly under nutrient-rich circumstances. Using both experiments and simulations, we find that a process akin to passive endocytosis can be recreated in model primitive cells. Molecules that are too impermeable to be absorbed can be taken up in a matter of seconds in an endocytic vesicle. The internalized cargo can then be slowly released over hours, into the main lumen or putative cytoplasm. This work demonstrates a way by which primitive life could have broken the symmetry of passive permeation prior to the evolution of protein transporters.

biophysics↗