Release of calcium from endolysosomes increases calcium influx through N-type calcium channels: Evidence for acidic store-operated calcium entry in neurons

Liang Hui, Nicholas H. Geiger, Duncan Bloor-Young, Grant C. Churchill, Jonathan D. Geiger, Xuesong Chen

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)617-627
Number of pages11
JournalCell Calcium
Volume58
Issue number6
DOIs
StatePublished - Dec 2015
Externally publishedYes

Keywords

  • Calcium
  • Endolysosomes
  • GPN
  • Lysosome exocytosis
  • N-type calcium channels
  • NAADP
  • Store-operated calcium entry

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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