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S-acylation of Ca2+ transport proteins : molecular basis and functional consequences

Published inBiochemical Society transactions, vol. 52, no. 1, p. 407-421
Publication date2024-02-28
Abstract

Calcium (Ca2+) regulates a multitude of cellular processes during fertilization and throughout adult life by acting as an intracellular messenger to control effector functions in excitable and non-excitable cells. Changes in intracellular Ca2+ levels are driven by the co-ordinated action of Ca2+ channels, pumps, and exchangers, and the resulting signals are shaped and decoded by Ca2+-binding proteins to drive rapid and long-term cellular processes ranging from neurotransmission and cardiac contraction to gene transcription and cell death. S-acylation, a lipid post-translational modification, is emerging as a critical regulator of several important Ca2+-handling proteins. S-acylation is a reversible and dynamic process involving the attachment of long-chain fatty acids (most commonly palmitate) to cysteine residues of target proteins by a family of 23 proteins acyltransferases (zDHHC, or PATs). S-acylation modifies the conformation of proteins and their interactions with membrane lipids, thereby impacting intra- and intermolecular interactions, protein stability, and subcellular localization. Disruptions of S-acylation can alter Ca2+ signalling and have been implicated in the development of pathologies such as heart disease, neurodegenerative disorders, and cancer. Here, we review the recent literature on the S-acylation of Ca2+ transport proteins of organelles and of the plasma membrane and highlight the molecular basis and functional consequence of their S-acylation as well as the therapeutic potential of targeting this regulation for diseases caused by alterations in cellular Ca2+ fluxes.

eng
Keywords
  • Ca2+ signalling
  • Ca2+-handling proteins
  • S-acylation
  • S-palmitoylation
  • Humans
  • Carrier Proteins / metabolism
  • Calcium / metabolism
  • Fatty Acids / metabolism
  • Neoplasms
  • Acylation
  • Acyltransferases / metabolism
Citation (ISO format)
NÉRÉ, Raphaël Gabriel Michel et al. S-acylation of Ca2+ transport proteins : molecular basis and functional consequences. In: Biochemical Society transactions, 2024, vol. 52, n° 1, p. 407–421. doi: 10.1042/BST20230818
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Article (Published version)
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ISSN of the journal0300-5127
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