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Department of Pharmacology

Shooting calcium at lysosomes

Peace Atakpa, working with Babu Thillaiappan, David Prole and Stefania Mataragka in Colin Taylor’s lab, has shown, using a variety of approaches including a novel genetically encoded Ca2+ sensor, that a specific intracellular channel selectively delivers Ca2+ to lysosomes...

Lysosomes recycle materials imported from outside the cell and obsolete materials from within. Ca2+ within lysosomes is important for these and other lysosomal functions, but it is not known how lysosomes acquire Ca2+. The authors used a low-affinity Ca2+ sensor targeted to the surface of lysosomes to demonstrate that inositol 1,4,5-trisphosphate receptors (IP3Rs), which are intracellular Ca2+ channels expressed in the endoplasmic reticulum (ER), selectively deliver Ca2+ to lysosomes. Optical imaging of cells expressing endogenously tagged IP3Rs further revealed that lysosomes hop between regions of the ER enriched in IP3Rs. Disrupting the contacts between lysosomes and ER prevents lysosomes from accumulating Ca2+. In their paper in Cell Reports, the authors conclude that the ER, by accumulating Ca2+ from the cytosol and then squirting it directly at lysosomes through IP3Rs, allows lysosomes to sequester Ca2+.

Atakpa P, Thillaiappan NB, Mataragka S, Prole DL & Taylor, CW (2018) IP3 receptors preferentially associate with ER-lysosome contact sites and selectively deliver Ca2+ to lysosomes. Cell Reports 25, 3180-3193