Its about endoplasmic Reticulum

1. ROLE OF ENDOPLASMIC RETICULUMIN PROTEIN
SYSTHESIS AND TRANSPORT
TO BE PRESENTED BY:
MONALISA BEHERA
M.Sc. (PREVIOUS)
DEPT. OF GENETICS AND PLANT
BREEDING

2. INTRODUCTION:
Cell is the structural and functional unit of all living organisms,
except viruses. Various structures are visible in a cell, under a
light microscope and some other electron microscope. Some of
the structures are ;
 Cell wall
 Plasma lemma or cell membrane
 Endoplasmic reticulum
 Ribosomes
 Mitochondria etc.,
Out of these organelles endoplasmic reticulum is a type
of organelle present in the cells of eukaryotic organisms that
forms an interconnected network of flattened, membrane-
enclosed sacs or tubes known cisternae.

3.  The membranes of the ER are continuous with the outer
membrane of the nuclear envelope.
 Endoplasmic reticulum occurs in most types of eukaryotic
cells, including the most primitive Giardia,[1] but is absent
from Red blood cells and spermatozoa.
 The primary function of the smooth ER is to serve as a
platform for the synthesis of lipids (fats), carbohydrate
(sugars) metabolism , and the detoxification of drugs and
other toxins.
 Tissues and organs that directly participate in these activities,
such as the liver, are enriched in smooth ER.

4.  Morphologically, the rough ER is studded with ribosomes that
participate in protein synthesis giving its "rough" appearance
when viewed with the electron microscope.
 The proteins synthesized on the ER are transported from the ER
membranes by small vesicles that pinch off the surface and
enter the Golgi membrane stack (cisternae). From the Golgi, the
proteins are transported to the cell surface or to
other organelles .

5. ENDOPLASMICRETICULUM: AN OVERVIEW
 The endoplasmic reticulum (ER) is a network of membrane-
enclosed tubules and sacs (cisternae) that extends from the
nuclear membrane throughout the cytoplasm.
 The entire endoplasmic reticulum is enclosed by a continuous
membrane and is the largest organelle of most eukaryotic
cells.
 Its membrane may account for about half of all cell
membranes, and the space enclosed by the ER (the lumen, or
cisternal space) may represent about 10% of the total cell
volume.

7.  There are two distinct types of ER that perform different
functions within the cell;
1. Smooth endoplasmic reticulum
2. Rough endoplasmic reticulum
 The rough ER, which is covered by ribosomes on its outer
surface, functions in protein processing. The smooth ER is
not associated with ribosomes and is involved in lipid, rather
than protein, metabolism.
 Rough ER is mainly composed of cisterns and is found in
cells actively involved in protein synthesis. Smooth and
Rough ER change into each other as per the needs of a cell.

9. ENDOPLASMIC RETICULUM IN PROTEIN
SYNTHESIS:-
 The binding site of the ribosome on the RER is the translocon.
[The translocon (commonly known as a translocator or translocation
channel) is a complex of proteins associated with the translocation of
polypeptides across membranes.]
 The role of the endoplasmic reticulum in protein processing and
sorting was first demonstrated by George Palade and his
colleagues in 1960s.
 However, the ribosomes bound to ER at any one time are not a stable
part of this organelle's structure as they are constantly being bound and
released from the membrane.
 A ribosome only binds to the RER once a specific protein-nucleic acid
complex forms in the cytosol.

10.  This special complex forms when a free ribosome begins translating
the mRNA of a protein destined for the secretory pathway.
 The first 5-30 amino acids polymerized encode a signal peptide, a
molecular message that is recognized and bound by a signal
recognition particle (SRP).
[The SRP is a small protein/RNA complex that acts as a targeting guide
and is essential for protein translocation into the rER lumen (interior
chamber)].
 Translation pauses and the ribosome complex binds to the
RER translocon where translation continues with the nascent protein
forming into the RER lumen and/or membrane.
 The protein is processed in the ER lumen by an enzyme (a
signal peptidase), which removes the signal peptide.

15.  Many proteins in yeast, as well as a few proteins in mammalian
cells, are targeted to the ER after their translation is complete
(posttranslational translocation), rather than being transferred into
the ER during synthesis on membrane-bound ribosomes.
 These proteins are synthesized on free cytosolic ribosomes, and
their posttranslational incorporation into the ER does not
require SRP.
 Instead, their signal sequences are recognized by distinct receptor
proteins (the Sec62/63 complex) associated with the Sec61
complex in the ER membrane .

16.  Cytosolic chaperones are required to maintain
the polypeptide chains in an unfolded conformation so they can
enter the Sec61 channel, and another chaperone within the ER
(called BiP) is required to pull the polypeptide chain through
the channel and into the ER.
The translocon complex consists of several large protein
complexes. The central element is the translocation channel
itself, the heterotrimer Sec61.

19. PROTEIN FOLDING:-
 The ER lumen maintains a chemical environment that ensures
that proteins are folded into the correct conformation .
(Misfolded proteins are useless and may cause problems if
they are detected as "foreign structures" by the immune
system of the body).
 Newly synthesized proteins are quickly associated with ER
"chaperone proteins" and folding enzymes that assist in the
folding of the proteins into their correct conformations.
For example, one of the major proteins within the ER lumen is a
member of the Hsp70 family of chaperones called BiP(Binding
immunoglobulin protein).

20. BiP is thought to bind to the unfolded polypeptide chain as it crosses the
membrane and then mediates protein folding and the assembly of
multisubunit proteins within the ER .
 Correctly assembled proteins are released from BiP and are
available for transport to the Golgi apparatus.
 Abnormally folded or improperly assembled proteins, however,
remain bound to BiP and are consequently retained within the
ER or degraded, rather than being transported farther along the
secretory pathway.
 It is not known exactly how the ER recognizes misfolded
proteins, but it may be able to recognize specific domains or
segments on the proteins.
For example, a hydrophobic domain (water-avoiding segment)
should be tucked away inside the protein, but a misfolded protein
may have this domain protruding outward. Such a protein would be
retained and degraded.

22. PROTEIN TRANSPORT
 Newly synthesized proteins enter the biosynthetic- secretory
pathway in the ER by crossing the ER membrane from
the cytosol.
 During their subsequent transport, from the ER to the Golgi
apparatus and from the Golgi apparatus to the cell surface and
elsewhere, these proteins pass through a series of compartments,
where they are successively modified.
 Transfer from one compartment to the next involves a delicate
balance between forward and backward (retrieval) transport
pathways. Some transport vesicles select cargo molecules and
move them to the next compartment in the pathway, while others
retrieve escaped proteins and return them to a previous
compartment where they normally function.

24.  Thus, the pathway from the ER to the cell surface involves many
sorting steps, which continually select membrane and soluble
lumenal proteins for packaging and transport—in vesicles
or organelle fragments that bud from the ER and Golgi apparatus.
 To initiate their journey along the biosynthetic-secretory pathway,
proteins that have entered the ER and are destined for the Golgi
apparatus or beyond are first packaged into small COPII-coated
transport vesicles.
 These transport vesicles bud from specialized regions of the ER
called ER exit sites, whose membrane lacks bound ribosomes. In
most animal cells, ER exit sites seem to be randomly dispersed
throughout the ER network.

25.  After transport vesicles have budded from an ER exit site and
have shed their coat, they begin to fuse with one another.
 This fusion of membranes from the same compartment is
called homotypic fusion, to distinguish it from heterotypic
fusion, in which a membrane from one compartment fuses with
the membrane of a different compartment.
 As with heterotypic fusion, homotypic fusion requires a set of
matching SNAREs.
[SNARE proteins (an acronym derived from "SNAP
(Soluble NSF Attachment Protein) Receptor") are a large protein
superfamily consisting of more than 60 members in yeast and
mammalian cells.[1] The primary role of SNARE proteins is to
mediate vesicle fusion, that is, the fusion of vesicles with their
target membrane bound compartments].

26.  In this case, however, the interaction is symmetrical, with v-
SNAREs and t-SNAREs contributed by both membranes.
SNAREs can be divided into two categories: vesicle or v-SNAREs,
which are incorporated into the membranes of transport vesicles
during budding, and target or t-SNAREs, which are located in the
membranes of target compartments.

29.  These clusters constitute a new compartment that is separate
from the ER and lacks many of the proteins that function in the
ER.
 They are generated continually and function as transport
packages that bring material from the ER to the Golgi apparatus.
The clusters are relatively short-lived because they quickly
move along microtubules to the Golgi apparatus, where they
fuse and deliver their contents.
 As soon as vesicular tubular clusters form, they begin budding
off vesicles of their own. Unlike the COPII-coated vesicles that
bud from the ER, these vesicles are COPI-coated. They carry
back to the ER resident proteins that have escaped, as well as
proteins that participated in the ER budding reaction and are
being returned.

31.  The retrieval (or retrograde) transport continues as the vesicular
tubular clusters move to the Golgi apparatus. Thus, the clusters
continuously mature, gradually changing their composition as
selected proteins are returned to the ER.
 A similar retrieval process continues from the Golgi apparatus,
after the vesicular tubular clusters have delivered their cargo.

32. REFERENCE
 Soltys, B.J., Falah, M.S. and Gupta, R.S. (1996) Identification
of endoplasmic reticulum in the primitive eukaryote Giardia
lamblia using cryoelectron microscopy and antibody to Bip. J.
Cell Science 109: 1909-1917.
 Levine T (September 2004). "Short-range intracellular
trafficking of small molecules across endoplasmic reticulum
junctions". Trends Cell Biol. 14 (9): 483–90
 Endoplasmic reticulum. (n.d.). McGraw-Hill Encyclopedia of
Science and Technology. Retrieved September 13, 2006, from
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