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A cellular atlas of calcineurin signaling

Idil Ulengin-Talkish1, Martha S Cyert1

  • 1Department of Biology, Stanford University, Stanford, CA 94035, United States.

Biochimica Et Biophysica Acta. Molecular Cell Research
|October 3, 2022
PubMed

Insights

Calcium (Ca2+) signals control cellular processes in specific locations. Calcineurin, a Ca2+-regulated phosphatase, has diverse roles beyond immunity, functioning in various cellular microdomains.

Area of Science:

  • Cell Biology
  • Biochemistry

Background:

  • Intracellular calcium (Ca2+) signals are precisely controlled in time and space, forming signaling microdomains.
  • Calcineurin (CN), a Ca2+/calmodulin-regulated protein phosphatase, is a target of immunosuppressants like Cyclosporin A and FK506.
  • While known for activating the adaptive immune response via NFAT dephosphorylation, CN's full functional scope is broader.

Approach:

  • This review systematically maps human CN substrates and regulators.
  • It emphasizes the spatial localization of CN signaling and its targeting mechanisms.
  • The role of short linear motifs (SLiMs) in targeting CN and substrates to signaling microdomains is discussed.

Key Points:

  • Calcineurin is ubiquitously expressed and involved in diverse cellular functions.
  • CN regulates events at multiple cellular locations, including the plasma membrane, intracellular membranes, mitochondria, nuclear pore complex, and centrosomes/cilia.
  • Signaling microdomains are crucial for localized CN activity, often mediated by specific peptide motif binding.

Conclusions:

  • A comprehensive cellular atlas of Ca2+/calcineurin signaling is presented, highlighting its widespread and localized functions.
  • Expanding knowledge reveals unexpected roles for calcineurin throughout the cell, beyond its established role in immune response.
  • Understanding localized CN actions is key to deciphering its versatile cellular functions.
Keywords:
CalcineurinCalciumPhosphatasePhosphorylationSLiMsSignaling

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