STIM1-induced precortical and cortical subdomains of the endoplasmic reticulum

Abstract

Store-operated calcium entry relies on the formation of a specialized compartment derived from the endoplasmic reticulum (ER) and closely apposed to the plasma membrane. In this study, detailed ultrastructural analysis revealed the existence of three distinct structures derived from conventional ER: precortical ER, cortical ER, and thin cortical ER. Precortical subdomains of the ER enriched in STIM1 can form without contacting the plasma membrane. Upon ER calcium depletion, these subdomains are translocated to the plasma membrane to form cortical ER, which is still connected to the conventional ER. Thin cortical ER, depleted of BiP and deprived of attached ribosomes, may represent a specialized region dedicated to calcium regulation and not engaged in protein translocation and folding. These observations form the basis for future structure-function analysis of cortical ER.calcium ͉ store-operated calcium entry

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

“…4B) . Extensive contact between the ER and the PM may also occur in animal cells, although the extent of contact has not been characterized by EM tomography, except under conditions that activate store-operated Ca 2þ release and during mitosis (McCullough and Lucocq 2005;Orci et al 2009). …”

Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

“…Although this interaction is weakened by store depletion and does not appear necessary for puncta formation (Grigoriev et al 2008), one could imagine that STIM1-laden ER tubules are propelled in this way toward the cell periphery by microtubules, and when they encounter local sites of elevated IP 3 , local ER depletion releases the tubule near the PM with STIM1 primed to interact with the PM and establish or stabilize a junction. Interestingly, in two EM studies, store depletion caused the number of ER-PM junctions to increase, and overexpression of STIM1 further amplified this effect Orci et al 2009). Microtubules have also been observed aligned with cortical ER, perhaps as a memory trace of the ER's journey to the PM (Orci et al 2009).…”

“…Interestingly, in two EM studies, store depletion caused the number of ER-PM junctions to increase, and overexpression of STIM1 further amplified this effect Orci et al 2009). Microtubules have also been observed aligned with cortical ER, perhaps as a memory trace of the ER's journey to the PM (Orci et al 2009). …”

“…These peripheral puncta correspond at the ultrastructural level to specialized regions of smooth ER positioned within 10 -20 nm of the plasma membrane, known as ER-PM junctions (Fig. 1B) Lur et al 2009;Orci et al 2009). In Jurkat T cells expressing ER-targeted horseradish peroxidase, electron microscopic studies show that native ER-PM junctions cover ,5% of the cell surface .…”

“…However, little is known about how ER-PM junctions form and disassemble. Depletion of stores and STIM1 overexpression increases the number and extent of ER-PM junctions Orci et al 2009), suggesting a role for STIM1 in their formation or stabilization. Similarly, overexpression or knockdown of the widely expressed SR/ER protein junctate increases or decreases the abundance of junctions, respectively, although this was store-independent (Treves et al 2004(Treves et al , 2010.…”