Acidic store-operated calcium entry in primary cultured neurons

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NCRR	NEURO/BEHAV/SENSYS-9

Authors

• L. Hui
• X. Chen
• B. Singh
• J.D. Geiger

Abstract

Endolysosomes are intracellular ‘acidic’ stores containing high concentrations of calcium. Although these ‘acidic calcium stores’ are present functionally in neurons, little is known about how the calcium released from the acidic stores contributes to calcium signals spatiotemporally. In primary cultured hippocampal neurons, we found that calcium released from acidic calcium stores (either inhibition of vacuolar H+-ATPase with bafilomycin or selective disruption of endolysosome membranes with GPN) triggered calcium influx across the plasma membrane, a phenomenon we termed ‘acidic store-operated calcium entry’ (aSOCE). To further investigate how acidic calcium stores communicate with plasma membrane, we hypothesize that calcium released from acidic calcium stores increases calcium influx through plasma membrane N-type calcium channels (NTCC). Our data showed that this aSOCE was attenuated significantly by blocking NTCC. Interestingly, bafilomycin or GPN increased cell surface expression of NTCC and LAMP1, a lysosome protein regulating lysosomal exocytosis. Further observations suggested a physical linkage between NTCC and LAMP1. Additionally, knocking down NTCC and LAMP1 attenuated aSOCE. Collectively, our findings suggest exocytotic insertion of N-type calcium channels might underlie this novel process of aSOCE in neurons. Such findings could provide a new insight into the spatiotemporal complexity of calcium signals and fundamental calcium-dependent cellular processes in neurons.

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