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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Calcium Tunneling: A Pervasive Signaling Module Mediated by Coupling Store-Operated Ca2+ Entry and Endoplasmic

Raphael Courjaret1, Khaled Machaca2

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Cells use calcium (Ca2+) tunneling to transmit signals to distant effectors. This process involves shuttling Ca2+ through the endoplasmic reticulum, overcoming spatial restrictions for precise cellular communication.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Intracellular calcium (Ca2+) signaling is crucial for cellular functions but faces spatial and temporal limitations.
  • Calcium entry via plasma membrane channels typically activates only nearby effectors.
  • Efficient signaling to distant cellular targets requires specialized mechanisms.

Purpose of the Study:

  • To review the mechanisms and functions of calcium tunneling.
  • To highlight recent findings on the role of cortical endoplasmic reticulum structure and membrane contact sites in calcium tunneling.
  • To discuss the organization of the machinery involved in calcium tunneling.

Main Methods:

  • Literature review of recent findings on calcium signaling and endoplasmic reticulum.
  • Analysis of structural data concerning cortical endoplasmic reticulum and membrane contact sites.
  • Examination of molecular mechanisms underlying calcium transport and release.

Main Results:

  • Calcium tunneling enables the targeted delivery of Ca2+ to distal cellular effectors.
  • The cortical endoplasmic reticulum acts as a conduit for Ca2+ shuttling.
  • Inositol 1,4,5-trisphosphate receptors play a role in releasing Ca2+ for distal signaling.

Conclusions:

  • Calcium tunneling is a vital mechanism for precise, long-range intracellular Ca2+ signaling.
  • The structure of the endoplasmic reticulum at membrane contact sites is integral to tunneling efficiency.
  • Understanding Ca2+ tunneling machinery offers insights into cellular communication and regulation.