TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry.

ABSTRACT: Lysosomes are membrane-bound organelles mainly involved in catabolic processes. In addition, lysosomes can expel their contents outside of the cell via lysosomal exocytosis. Some of the key steps involved in these important cellular processes, such as vesicular fusion and trafficking, require calcium (Ca²⁺) signaling. Recent data show that lysosomal functions are transcriptionally regulated by transcription factor EB (TFEB) through the induction of genes involved in lysosomal biogenesis and exocytosis. Given these observations, we investigated the roles of TFEB and lysosomes in intracellular Ca²⁺ homeostasis. We studied the effect of transient modulation of TFEB expression in HeLa cells by measuring the cytosolic Ca²⁺ response after capacitative Ca²⁺ entry activation and Ca²⁺ dynamics in the endoplasmic reticulum (ER) and directly in lysosomes. Our observations show that transient TFEB overexpression significantly reduces cytosolic Ca²⁺ levels under a capacitative influx model and ER re-uptake of calcium, increasing the lysosomal Ca²⁺ buffering capacity. Moreover, lysosomal destruction or damage abolishes these TFEB-dependent effects in both the cytosol and ER. These results suggest a possible Ca²⁺ buffering role for lysosomes and shed new light on lysosomal functions during intracellular Ca²⁺ homeostasis.

SUBMITTER: Sbano L 

PROVIDER: S-EPMC5233950 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature