Release of calcium from endolysosomes increases calcium influx through N-type calcium channels: Evidence for acidic store-operated calcium entry in neurons. Issue 6 (December 2015)

• Record Type: Journal Article
• Authors: Hui, Liang; Geiger, Nicholas H.; Bloor-Young, Duncan; Churchill, Grant C.; Geiger, Jonathan D.; Chen, Xuesong
• Is Part Of: Cell calcium. Volume 58:Issue 6(2015)
• Page Start: 617
• Page End: 627
• Publication Date: 2015-12
• Subjects: Calcium -- Endolysosomes -- N-type calcium channels -- Lysosome exocytosis -- GPN -- NAADP -- Store-operated calcium entry; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2015.10.001
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: Acidic store-operated calcium entry (aSOCE) triggers calcium influx across plasma membranes. aSOCE is a process independent of endoplasmic reticulum calcium release. aSOCE is mediated at least in part by N-type calcium channels. N-type calcium channels interact with LAMP1 and knocking down LAMP1 attenuated aSOCE. Abstract: Neurons possess an elaborate system of endolysosomes. Recently, endolysosomes were found to have readily releasable stores of intracellular calcium; however, relatively little is known about how such 'acidic calcium stores' affect calcium signaling in neurons. Here we demonstrated in primary cultured neurons that calcium released from acidic calcium stores triggered calcium influx across the plasma membrane, a phenomenon we have termed "acidic store-operated calcium entry (aSOCE)". aSOCE was functionally distinct from store-operated calcium release and calcium entry involving endoplasmic reticulum. aSOCE appeared to be governed by N-type calcium channels (NTCCs) because aSOCE was attenuated significantly by selectively blocking NTCCs or by siRNA knockdown of NTCCs. Furthermore, we demonstrated that NTCCs co-immunoprecipitated with the lysosome associated membrane protein 1 (LAMP1), and that aSOCE is accompanied by increased cell-surface expression levels of NTCC and LAMP1 proteins. Moreover, we demonstrated that siRNA knockdown of LAMP1 or Rab27a, both of which are key proteins involved in lysosome exocytosis, attenuated significantly aSOCE. Taken together our data suggest that aSOCE occurs in neurons, that aSOCE plays an important role in regulating the levels and actions of intraneuronal calcium, and that aSOCE is regulated at least in part by exocytotic insertion of N-type calcium channels into plasma membranes through LAMP1-dependent lysosome exocytosis.