Is all of the endoplasmic reticulum created equal? The effects of the heterogeneous distribution of endoplasmic reticulum Ca2+-handling proteins

Abstract

The endoplasmic reticulum is a heterogeneous compartment with respect to the distribution of its Ca2+-handling proteins, namely the Ca2+-binding proteins, the Ca2+ pumps and the Ca2+ release channels. The nonuniform distribution of these proteins may explain the functional heterogeneity of the endoplasmic reticulum, such as the generation of spatially complex Ca2+ signals, Ca2+ homeostasis, and protein folding and quality control.

Figure 1.

The distribution of Ca ²⁺ -binding proteins within the endoplasmic reticulum of mouse embryonic fibroblasts, in relation to calreticulin (CRT), as shown by double immunofluorescence labeling and visualized by confocal microscopy. For methods, see Mesaeli et al. (1999). Left to right: CRT distribution (red), PDI, or Grp94 distribution (green). The last column of each row is an overlay of the two previous images; yellow represents areas of overlap. (A) The distributions of CRT and PDI are overlapping yet distinct. Note the green areas indicative of PDI localization only. (B) The distribution of Grp94 shows virtually complete overlap compared with that of CRT.

Figure 2.

Human oocytes showing distribution of calreticulin (CRT), calnexin (CNX), and calsequestrin (CSQ). CRT predominates in the cell cortex; CNX is also in the cell cortex, but in a trilaminar arrangement; and finally, CSQ is found spread throughout the cell.