Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration - International Review of Cell and Molecular Biology - page 216

the observation of the preferential localization of vesicular elements in the
perinuclear region of the cytoplasm, known as endoplasm ( Palade, 1956 ).
Early studies described two major types of membranous structures of ER,
distinguishable by their biochemical and morphologic properties and their
sedimentation features. One type corresponds to the tubular or “tadpole-
like” structure recovered in the low-density fraction, and the other to the
spherical vesicles present in the high-density fraction ( Heuson-Stiennon
et al., 1972 ).
The ER, although frequently associated with the cellular exo-endo-
cytic pathway, is a complex organelle in terms of both its structure and
function ( Fig. 5.1 ). It plays critical roles in a wide range of processes,
including (a) synthesis, folding, modification, and transport of proteins;
(b) synthesis and distribution of phospholipids and steroids; (c) storage of
calcium ions within its lumen and their regulated release into the cyto-
plasm ( Schröder, 2008 ). Perturbations in any of these functions results
in ER stress and aggregation of misfolded proteins. ER stress has been
observed during physiological conditions, such as nutrient deprivation
and the differentiation of type B lymphocytes into plasma cells, as well as
in pathological conditions, such as viral infection, ischemia/reperfusion
and cardiomyocyte hypertrophy.
2. STRUCTURE, FUNCTION AND DYNAMICS OF
ENDOPLASMIC RETICULUM
2.1. General Structure of Endoplasmic Reticulum
2.1.1. Rough ER Sheets and Smooth ER Tubules
A number of approaches have established that the ER is a continuous com-
partment extending from nucleus to cytosol. Based on its structure, the ER
is classically subdivided in the ribosome-studded rough endoplasmic reticu-
lum (RER) and the ribosome-free smooth endoplasmic reticulum (SER)
( English et al., 2009 ). Cells that secrete large amounts of protein are rich in
RER, while steroid-synthesizing and muscle cells have abundant SER. In
many cells, RER and SER do not occupy spatially segregated regions; how-
ever, in some cells such as hepatocytes and neurons, the smooth and rough
portions of the ER occupy different cellular areas ( Borgese et al., 2006 ).
The SER morphology differs from that of RER by its typically more com-
plex, tubular network and greater numbers of branch points. Xenobiotic-
metabolizing enzymes are also preferentially located in the SER ( Orrenius
and Ericsson, 1966 ).