Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance

Koffi L. Lakpa, Peter W. Halcrow, Xuesong Chen, Jonathan D. Geiger

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Neurons are long-lived post-mitotic cells that possess an elaborate system of endosomes and lysosomes (endolysosomes) for protein quality control. Relatively recently, endolysosomes were recognized to contain high concentrations (400–600 μM) of readily releasable calcium. The release of calcium from this acidic organelle store contributes to calcium-dependent processes of fundamental physiological importance to neurons including neurotransmitter release, membrane excitability, neurite outgrowth, synaptic remodeling, and cell viability. Pathologically, disturbances of endolysosome structure and/or function have been noted in a variety of neurodegenerative disorders including Alzheimer’s disease (AD) and HIV-1 associated neurocognitive disorder (HAND). And, dysregulation of intracellular calcium has been implicated in the neuropathogenesis of these same neurological disorders. Thus, it is important to better understand mechanisms by which calcium is released from endolysosomes as well as the consequences of such release to inter-organellar signaling, physiological functions of neurons, and possible pathological consequences. In doing so, a path forward towards new therapeutic modalities might be facilitated.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages681-697
Number of pages17
DOIs
StatePublished - 2020
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1131
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Alzheimer’s disease
  • Calcium
  • Endolysosomes
  • Endosomes
  • HIV-1 associated neurocognitive disorder
  • Lysosomes
  • N-type calcium channels
  • Neurodegenerative diseases
  • Neurons
  • Store-operated calcium entry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Lakpa, K. L., Halcrow, P. W., Chen, X., & Geiger, J. D. (2020). Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance. In Advances in Experimental Medicine and Biology (pp. 681-697). (Advances in Experimental Medicine and Biology; Vol. 1131). Springer New York LLC. https://doi.org/10.1007/978-3-030-12457-1_27