Ca²⁺ Channels on the Move

Abstract

The versatility of Ca2+ as an intracellular messenger derives largely from the spatial organization of cytosolic Ca2+ signals, most of which are generated by regulated openings of Ca2+-permeable channels. Most Ca2+ channels are expressed in the plasma membrane (PM). Others, including the almost ubiquitous inositol 1,4,5-trisphosphate receptors (IP3R) and their relatives, the ryanodine receptors (RyR), are predominantly expressed in membranes of the sarcoplasmic or endoplasmic reticulum (ER). Targeting of these channels to appropriate destinations underpins their ability to generate spatially organized Ca2+ signals. All Ca2+ channels begin life in the cytosol, and the vast majority are then functionally assembled in the ER, where they may either remain or be dispatched to other membranes. Here, by means of selective examples, we review two issues related to this trafficking of Ca2+ channels via the ER. How do cells avoid wayward activity of Ca2+ channels in transit as they pass from the ER via other membranes to their final destination? How and why do some cells express small numbers of the archetypal intracellular Ca2+ channels, IP3R and RyR, in the PM?

Ca2+ signalling early in evolution – all but primitive

“…Both types of CRC are closely related and share some characteristic features (Taylor et al, 2004;Taylor et al, 2009;Boehning, 2010;Seo et al, 2012). However, CRCs have not been identified in many unicellular organisms or in plants (Gillaspy, 2011).…”

IP3 Receptors: Toward Understanding Their Activation

“…If we are to understand how Ca 2þ functions as a ubiquitous intracellular messenger, we must explain how IP 3 -evoked Ca 2þ signals grow from the opening of a single IP 3 R to much larger events. That explanation depends, ultimately, on putting IP 3 R into appropriate places within the cell, and on the interactions between IP 3 and Ca 2þ in regulating the opening of IP 3 R. In recent reviews (Taylor et al 2009a;Taylor et al 2009b) and original reports, we have described how IP 3 R are co-translationally targeted to the ER and then retained there by sequences within their transmembrane domains (TMD) (Parker et al 2004;Pantazaka and Taylor 2010). We have also suggested that within the ER, IP 3 causes IP 3 R to assemble into small clusters within which their regulation by both IP 3 and Ca 2þ is retuned to facilitate the Ca 2þ -mediated recruitment of IP 3 R activity by an active neighbor ).…”

La signalisation calcique dans les lymphocytes T

“…Récepteurs IP3, Ca 2+ blips et Ca 2+ puffs Les RIP3 sont exprimés dans la plupart des cellules animales et sont un lien essentiel entre de nombreux récepteurs à la membrane plasmique qui stimulent la PLC et la libéra-tion de stocks intracellulaires de Ca 2+ [7][8][9]. Chez les mammifères, les trois types de RIP3 sont structurellement proches et s'assemblent en homo ou hétérotétramères pour former des canaux calciques intracellulaires.…”

“…Weber et al [6] montrent que le pic initial de réponse calcique à la suite de l'engagement du TCR est le même dans les Th1, Th2 et les Th17, [8,12]. Il est à noter que l'augmentation de la libération de Ca 2+ générant les puffs n'est pas due à une augmentation directe de la quantité de calcium libérée par les RIP3, mais à l'augmentation de la fréquence d'ouverture de ces canaux [7].…”