Neglected wardens: T lymphocyte ryanodine receptors

Research output: Contribution to journalReview articlepeer-review

Abstract

Ryanodine receptors (RyRs) are intracellular Ca2+ release channels ubiquitously expressed in various cell types. RyRs were extensively studied in striated muscle cells due to their crucial role in muscle contraction. In contrast, the role of RyRs in Ca2+ signalling and functions in non-excitable cells, such as T lymphocytes, remains poorly understood. Expression of different isoforms of RyRs was shown in primary T cells and T cell lines. In T cells, RyRs co-localize with the plasmalemmal store-operated Ca2+ channels of the Orai family and endoplasmic reticulum Ca2+ sensing Stim family proteins and are activated by store-operated Ca2+ entry and pyridine nucleotide metabolites, the intracellular second messengers generated upon stimulation of T cell receptors. Experimental data indicate that together with d-myo-inositol 1,4,5-trisphosphate receptors, RyRs regulate intercellular Ca2+ dynamics by controlling Ca2+ concentration within the lumen of the endoplasmic reticulum and, consequently, store-operated Ca2+ entry. Gain-of-function mutations, genetic deletion or pharmacological inhibition of RyRs alters T cell Ca2+ signalling and effector functions. The picture emerging from the collective data shows that RyRs are the essential regulators of T cell Ca2+ signalling and can be potentially used as molecular targets for immunomodulation or T cell-based diagnostics of the disorders associated with RyRs dysregulation.

Original languageEnglish (US)
Pages (from-to)4415-4426
Number of pages12
JournalJournal of Physiology
Volume599
Issue number19
DOIs
StatePublished - Oct 1 2021

Keywords

  • cell-based diagnostics
  • cytosolic Ca
  • immunomodulation
  • Orai
  • ryanodine receptor
  • Stim
  • T lymphocytes

ASJC Scopus subject areas

  • Physiology

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