endoplasmic reticulam

1. • Endoplasmic reticulum (ER) is a vast network of membrane-bound,
branching and interconnecting tubules, vesicles and flattend sacs,
irregularly distributed in the cytoplasmic matrix.
• With the exception of prokaryotes and mature mammalian erythrocytes, it is
present in almost all kinds of cells.
• It is only poorly developed in egg cells, sperm cells and undifferentiated and
rapidly dividing embryonic cells and cancer cells.
• Generally, it is very simple in those cells which actively engage in lipid
metabolism (e.g., adipose cells, brown fat cells, adrenocortical cells, etc.),
but complex and extensive in protein synthetically active cells.

2. ENDOPLASMIC RETICULUM

3. Discovery
• The first fruitful investigations about ER were made by Garnier (1897).
• He could observe a basophilic fibrillar material in stained cells.
• It was later on termed ergastoplasm.
• With the help of electron microscope, Porter, Thompson, Claude and
Fullam (1945) observed a lace-like network of membranes within the
cytoplasm.
• It was termed endoplasmic reticulum by Porter and Kallman (1952).

4. Morphology
• ER is a complex system of membrane-bound spaces.
• These spaces are filled with a fluid,. rich in enzymes, metabolites and synthetic
products.
• There are two kinds of ER, namely granular or rough -surfaced ER (RER) and
agranular or smooth-surfaced ER (SER).
• RER has attached ribosomes, and SER has no attached ribosomes.
• RER is the major location for the synthesis of secretory or export proteins and
the protein constituents of ER.
• It is mainly concerned with the assembling, storage, processing and export of
secretory proteins.
• So, it is most extensive in cells which are active in the synthesis of secretory
proteins (e.g., enzyme-secreting cells, liver cells, pancreatic acinar cells).

6. • SER is mainly concerned with the synthesis of non-protein substances, mainly
lipids (such as (glycerides, glycolipids, phospholipids, sterols, etc.).
• It is also involved in the chemical modification of low molecular weight
substances (e.g., modification of sterols to steroid hormones), cellular
detoxification mechanisms and the formation of transport vesicles, which
carry proteins and lipids to Golgi bodies for chemical processing and
packaging.
• So, it predominantly occurs in cells, which actively engage in the synthesis of
lipids (e.g., adipose cells, interstitial cells of testis, adrenocortical cells, etc.).

7. • ER exists in three morphologically different forms, namely lamellae, vesicles and
tubules.
• Lamellae are unbranched and flattened sacs, arranged in parallel stacks. Their
internal lumen is called cisterna.
• Vesicles are closed oval or rounded sacs. They are found in large numbers in liver
cells and pancreatic cells.
• Tubules are branching and interconnecting units, much abundant in cells which are
active in the synthesis of steroids.
• Vesicles and tubules are mostly agranular, whereas lamellae are granular.
• The lamellar and tubular units may merge together to form a continuous network.
When cells are homogenized, their ER may get fragmented.
• These fragments soon get reorganized forming small vesicles, called microsomes.
• Quite often, the components of ER perform sweeping movements within the cell.
• This brings about the distribution of substances and the molecular exchanges
between the cytoplasmic matrix and the contents of ER.

10. Chemical make-up and molecular
organization of ER
• The membranes of ER have lipoprotein composition and fluid-mosaic organization.
• They are formed mostly of phospholipids, cholesterol and intrinsic and extrinsic
proteins.
• Phospholipids form a bilayer.
• Cholesterol binds with this bilayer to form a stable complex.
• Intrinsic proteins partially or completely penetrate the lipid bilayer, whereas
extrinsic proteins remain entirely outside the lipid bilayer.
• Intrinsic proteins are mostly structural, and extrinsic proteins are mostly enzymatic.
• There are two characteristic transmembrane structural glycoproteins in the RER,
namely ribophorins I & II (absent in SER).
• They serve as the binding sites for ribosomes, and also mediate the binding of
ribosome with RER.
• Ribophorins interact with each other and form a network within the membrane to
control the distribution of ribosome binding sites.

12. • The protein to lipid ratio is much higher, and the cholesterol content is very low
in the ER membranes than in plasma membrane.
• The high protein content (50-70%) gives the membrane structural stability
(possibly by immobilizing most of the amphipathic lipid molecules), and the low
lipid content makes the membrane less fluid.
• ER membranes do not have lamellar organization every where.
• In some regions they are lamellar, and in some other parts micellar (globular).
• Micellar regions are probably the dynamic regions of fission and fusion.
• The combination of lamellar and micellar organization may permit drastic
changes in the surface area of the membrane.

13. Biogenesis
• The origin of ER is not clearly understood.
• Still, it is believed that a cell receives a full set of membranes from its
parent cell, and also that ER is "budded" off from nuclear envelope by
a process of evagination (the nuclear envelope, in turn, is believed to
take its origin from vesicular ER during telophase).
• RER is believed to appear first, and later it gives rise to SER.

14. • The biogenesis of ER involves two major steps, namely membrane synthesis
and membrane differentiation.
• The former involves the initial synthesis of a basic framework of lipids and
intrinsic proteins, and the latter involves the chemical modification of this
framework by the incorporation of additional constituents.
• Membrane differentiation includes structural and functional modifications.
Structural modification includes the incorporation of structural lipids and
proteins.
• Functional modification includes the introduction of enzymes and other
functional proteins and some specific sugars.
• Evidences suggest that the introduction of each kind of molecule is
independent of the others.
• Most of the ER proteins are synthesised on the ER-bound ribosomes, and a few
on free cytoribosomes.

15. • The budding of ER from nuclear envelope a outer nuclear membrane
gives out finger-shaped off and get into the cytosol and form vesicles
called blebs. This is called blebbing.
• Blebs soon migrate to the periphery of the cell, get arranged in rows
and fuse to form stack of double membrane sheets, called annulate
lamellae.
• These lamellae are similar to the nuclear envelope in having pores,
annuli and annular and central granules.
• They probably represent an intermediate stage in the formation of ER.
• Gradually, they lose their pores, get studded with attached ribosomes,
and then transform to RER.

18. Enzymatic properties
• The fluid that fills the lumen of ER contains a variety of enzymes
which, in general, are concerned with the following functions:
• (i) synthesis of glycerides, fatty acids, phospholipids, glycolipids and
steroids
• (ii) metabolism of plasmalogens (a kind of phospholipids)
• (iii) steroid transformation, aromatisation, hydroxylation,
deamination, thioester oxidation, drug detoxification, etc.
• (iv) dephosphorylation of UDP glucose.

19. Functions
• ER is actively involved in several mechanical and physiological functions
of the cell.
• Its major functions are the following:
• (i) Provides a structural framework and a supplementary mechanical
support to the colloidal cytoplasmic matrix, and also serves as an
intracellular transport system.
• (ii) Segregation, distribution and association of enzyme systems.
• (iii) Collection, storage, chemical processing and intracellular transport
of secretory proteins.
• (iv) Regulation of the intracellular exchange of materials, probably by
serving as diffusion barriers.

21. • (v) Regulation of ionic gradients, membrane potential and intracellular pH.
• (vi) Synthesis of phospholipids, lipoproteins, glycerides, sterols, steroid
hormones, bile acids, etc. (by SER).
• (vii) Chemical processing of nascent polypeptides (by RER)
• (viii) Glycosylation (complexing with oligosaccharides) of nascent proteins to
form glycoproteins, with the help of the enzyme oligosaccharyl transferase.
• (ix) Selective uptake, storage and release of Cat and the intracellular
transmission of impulses in striated muscles (by sarcoplasmic reticulum).
• (x) Secretion of chloride ions in the oxyntic (acid - secreting) parietal cells of
the gastric glands of vertebrate animals.

22. • .(xi) Enzymatic detoxification of harmful exogenous or endogenous substances
(by SER), mainly lipid-soluble poisons, drugs, anaesthetics, insecticides,
petroleum products, carcinogens, etc.
• (xii) Metabolism of vitamin A and the synthesis of visual pigments from it (in
the retinal cells of vertebrate animals).
• (xiii) Transport of RNAs and ribonucleoproteins from nucleus to cytoplasm.
• (xiv) Enzymatic dephosphorylation of glucose-6 phosphate to form free
glucose (glucogenesis), with the help of the enzyme glucose-6 phosphatase.
• (xv) Enzymatic detoxification of toxic metabolic products and drugs and lipid-
soluble poisons (in SER).

23. Sarcoplasmic reticulum(SR)
• SR is the extensive network of specialized SER, found in striated muscles.
• It consists of extensively branched membranous sacs, which enclose spaces
comparable to the cisternae of ER.
• SR surrounds each myofibril.
• At the two ends of each sarcomere (muscle segment), it bears expansions called
terminal cisternae.
• Typically, SR consists of three components, namely transverse, longitudinal and
junctional.
• The transverse component, also called T-system, is connected to the plasma
membrane of the muscle cell.
• The longitudinal component surrounds the muscle cell, and the junctional
component connects together the other two components.
• SR is mainly concerned with the storage of Ca++ ions.
• When the muscle is in the unexcited resting state, its membranes are impermeable to
Cat+ ions.

26. • Then the longitudinal component of the SR takes up Ca ions from the cytosol
by an active transport mechanism, called calcium pump or calcium - ATPase
transport system.
• These Ca ions are stored in the SR with the help of calcium-binding proteins.
• When the muscle fibres get excited by a nerve impulse, the calcium-
permeability of their SR increases and the calcium pump stops functioning.
• As a result, the Ca ions, stored in the cisternae of SR, are quickly released to
the sarcoplasm as a second messenger.
• This triggers muscular contraction. Once the elicitation of the nerve impulse
stops, the membranes of the SR quickly become impermeable to Ca ions.
• Now, calcium pump operates again, resulting in the accumulation of Ca++ ions
in the SR and the relaxation of the muscle.
• One ATP molecule is spent for the active transport of two Ca ions into the SR.