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Store-operated Ca²⁺-entry and adenylyl cyclase.

Dermot M F Cooper1

  • 1Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom.

Cell Calcium
|May 17, 2015
PubMed
Summary

Store-operated calcium entry (SOCE) selectively regulates calcium-sensitive adenylyl cyclase (AC) activity. The source of calcium, not the rise magnitude, determines AC responsiveness, with the molecular basis for AC8 now resolved.

Keywords:
Adenylyl cyclaseCalciumCalmodulinOrai1SOCEStim1

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Area of Science:

  • Cellular biology
  • Molecular signaling
  • Calcium signaling

Background:

  • Store-operated calcium entry (SOCE) is a critical calcium influx pathway.
  • SOCE selectively regulates calcium-sensitive adenylyl cyclase (AC) activity in non-excitable cells.
  • The precise mechanism linking SOCE to AC activity has been a long-standing question.

Purpose of the Study:

  • To elucidate the molecular basis for SOCE-dependent regulation of adenylyl cyclase 8 (AC8).
  • To investigate the role of calcium signaling microdomains centered on ACs.
  • To highlight the under-studied physiological relevance of SOCE regulation of ACs.

Main Methods:

  • Utilized calcium and cAMP sensors targeted to adenylyl cyclases.
  • Investigated the differential contribution of calcium source versus magnitude to AC responsiveness.
  • Focused on adenylyl cyclase 8 (AC8) as a model system.

Main Results:

  • Demonstrated that the source of calcium influx (SOCE) confers adenylyl cyclase responsiveness, not the magnitude of the calcium rise.
  • Resolved the molecular basis for SOCE-dependent regulation of AC8.
  • Characterized signaling microdomains associated with ACs using targeted sensors.

Conclusions:

  • The molecular basis for SOCE's selective regulation of AC8 activity is now understood.
  • Signaling microdomains around ACs play a crucial role in mediating SOCE effects.
  • Further research is needed to explore the broader physiological implications of SOCE regulation of ACs.