Cholesterol and Steroid Synthesizing Smooth Endoplasmic Reticulum of Adrenocortical Cells Contains High Levels of Proteins Associated with the Translocation Channel

Abstract

Steroid-secreting cells are characterized by abundant smooth endoplasmic reticulum whose membranes contain many enzymes involved in sterol and steroid synthesis. Yet they have relatively little morphologically identifiable rough endoplasmic reticulum, presumably required for synthesis and maintenance of the smooth membranes. In this study, we demonstrate that adrenal smooth microsomal subfractions enriched in smooth endoplasmic reticulum membranes contain high levels of translocation apparatus and oligosaccharyltransferase complex proteins, previously thought confined to rough endoplasmic reticulum. We further demonstrate that these smooth microsomal subfractions are capable of effecting cotranslational translocation, signal peptide cleavage, and N-glycosylation of newly synthesized polypeptides. This shifts the paradigm for distinction between smooth and rough endoplasmic reticulum. Confocal microscopy revealed the proteins to be distributed throughout the abundant tubular endoplasmic reticulum in these cells, which is predominantly smooth surfaced. We hypothesize that the broadly distributed translocon and oligosaccharyltransferase proteins participate in local synthesis and/or quality control of membrane proteins involved in cholesterol and steroid metabolism in a sterol-dependent and hormonally regulated manner.

Proteomic Landscape of Aldosterone-Producing Adenoma

“…26 The role of N-glycosylation in the adrenal cortex has not been studied in detail, although the modification is prominent in adrenocortical cells and has been postulated to affect local synthesis and quality control of membrane proteins involved in cholesterol and steroid metabolism. 27 Key regulators of steroidogenesis, MC2R and AT1R (receptors for ACTH and Ang II, respectively), are N-glycosylated and their activity could be affected by glycosylation. Similarly, lipoprotein receptors (LDLR and SR-B1) and many ion channels affecting steroidogenesis (TASK1, TASK3, TREK1, Kv1.4, CACNA1D) are N-glycoproteins and their levels/activities could be affected by increased glycosylation.…”

Endoplasmic Reticulum Ca2+Handling in Excitable Cells in Health and Disease

“…The amount of each type of ER and their structural organization vary considerably among different types of cells. For example, smooth ER is abundant in adrenocortical cells that produce glucocorticoids (cortisol in humans and corticosterone in rodents) (Black et al, 2005). In contrast, endocrine secretory cells that produce and release large amounts of protein and peptide hormones possess large amounts of rough ER (Bendayan, 1989).…”

Progressive sheet-to-tubule transformation is a general mechanism for endoplasmic reticulum partitioning in dividing mammalian cells

“…, 2009; Ueno et al. , 2010), whereas lipid and steroid synthesis and detoxification promote abundant tubular smooth ER (Black et al. , 2005).…”