Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release

Abstract

The versatility and universality of Ca 2 þ signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca 2 þ signalling is well studied in the microdomain scale, close to a Ca 2 þ channel, and at the whole-cell level. However, little is known about how local Ca 2 þ signals are regulated to specifically activate spatially distant effectors without a global Ca 2 þ rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP 3 ) receptor, SERCA pump and store-operated Ca 2 þ entry (SOCE) allows for efficient mid-range Ca 2 þ signalling. Ca 2 þ flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP 3 Rs to activate distal Ca 2 þ -activated Cl À channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP 3 R limits local Ca 2 þ diffusion and funnels Ca 2 þ through the ER lumen to activate a spatially separate Ca 2 þ effector.

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

“…in a way similar to the STIM1–Orai1 complexes assembly in response to store depletion). The latter possibility was recently inferred by Courjaret & Machaca (2014). Our data suggest that ANO1 itself can interact with the IP 3 Rs but we do not know yet if such an interaction is constitutive.…”

“…3 but cf. Courjaret & Machaca, 2014). The list of plausible candidates can surely be continued and we hope that future research will soon identify which of these are genuine.…”

A STIM1-dependent ‘trafficking trap’ mechanism regulates Orai1 plasma membrane residence and Ca2+ influx levels

“…5D,J), and importantly show that the translocation of intracellular Orai1 to the plasma membrane following store depletion is functionally coupled to increased levels of Ca 2+ influx through SOCE. (Courjaret and Machaca, 2014;Dolmetsch et al, 1997;Kar et al, 2012Kar et al, , 2014Parekh, 2009). SOCE levels depend on the stoichiometry of STIM1 and Orai1 in plasma membrane clusters (Hoover and Lewis, 2011), and as such on the levels of Orai1 at the plasma membrane.…”

The Ca2+-activated Cl− channel Ano1 controls microvilli length and membrane surface area in the oocyte

“…To increase intracellular Ca 2+ and stimulate Ano1, we mobilized intracellular Ca 2+ stores using ionomycin, and recorded Cl − currents at the peak of the Ca 2+ release phase (Courjaret and Machaca, 2014). As illustrated in Fig.…”