Endomembrane system
Submitted to- Submitted by- Preeti Saini
Dr. Jyoti Prakash R.NO.- 21mslsmm06
Department of Zoology Department of Human Genetics and Molecular
Central University of Punjab Medicine
Central University of Punjab
Contents-
• INTRODUCTION
• WHAT IS ENDOMEMBRANE SYSTEM
• COMPONENTS OF ENDOMEMBRANE SYSTEM
ENDOPLASMIC RETICULUM
GOLGI BODY
LYSOSOMES
VESICLES
• CONCLUSION
• REFERNCES
Introduction
• Cells have extensive sets of intracellular membranes, which together
compose the endomembrane system. The endomembrane system was
first discovered in the late 1800s when scientist Camillo Golgi noticed that
a certain stain selectively marked only some internal cellular membranes.
• Golgi thought that these intracellular membranes were interconnected,
but advances in microscopy and biochemical studies of the various
membrane-encased organelles later made it clear the organelles in the
endomembrane system are separate compartments with specific
functions.
• These structures do exchange membrane material, however, via a special
type of transport.
What is Endomembrane System?
• The endomembrane system (endo = “within”) is a
group of membranes and organelles in eukaryotic
cells that works together to modify, package, and
transport lipids and proteins.
• It includes the nuclear envelope, lysosome, the
endoplasmic reticulum and Golgi apparatus.
• The plasma membrane is included in the
endomembrane system because it interacts with the
other endomembranous organelles.
• Note- The endomembrane system does not include
the membranes of either mitochondria or
chloroplasts.
Components of Endomembrane system
ENDOPLASMIC RETICULUM
• It consists of a network of membranous tubules and flattened sacs.
• The discs and tubules of the ER are hollow, and the space inside is called the lumen.
• The membrane of the ER, which is a phospholipid bilayer embedded with proteins,
is continuous with the nuclear envelope.
• Membranous sacs and tubules that collectively modifies proteins and synthesizes
lipids.
• However, these two functions are performed in separate areas of the ER: the rough
ER and the smooth ER, respectively.
Rough Endoplasmic Reticulum
• The rough endoplasmic reticulum (RER)
is so named because the ribosomes
attached to its cytoplasmic surface give it
a studded appearance when viewed
through an electron microscope.
• Rough ER lies immediately adjacent to the
cell nucleus, and its membrane is
continuous with the outer membrane of
the nuclear envelope.
• The RER is also located near the Golgi
apparatus, which transports, modifies,
and packages proteins for delivery to
targeted destinations.
• Many proteins that are synthesized in the
RER are packaged into vesicles and
transported to the Golgi apparatus.
Functions of Rough Endoplasmic Reticulum
• Inside the ER, the proteins fold and undergo modifications, such as the
addition of carbohydrate side chains. These modified proteins will be
incorporated into cellular membranes—the membrane of the ER or those of
other organelles—or secreted from the cell.
• The RER also makes phospholipids for cellular membranes.If the
phospholipids or modified proteins are not destined to stay in the RER, they
will reach their destinations via transport vesicles that bud from the RER’s
membrane.
• It is also responsible for the metabolism of carbohydrates.
• Since the rough ER helps modify proteins that will be secreted from the cell,
cells whose job is to secrete large amounts of enzymes or other proteins, such
as liver cells, have lots of rough ER.
Smooth Endoplasmic Reticulum
• The smooth endoplasmic reticulum (smooth ER) is a membranous organelle found in
most eukaryotic cells. It is a subset of the endomembrane system of the endoplasmic
reticulum.
• The smooth endoplasmic reticulum is primarily composed of three-dimensional
polygonal networks of tubules called cisternae.
• The high curvature of these structures needs to be stabilized by many proteins,
including reticulons, DP1 and receptor expression enhancing proteins (REEPs). These
proteins either bend the membrane through structural elements that wedge
themselves into the lipid bilayer or shape the membrane through oligomerization.
• The smooth ER is also a dynamic structure, with new tubules budding off from the
sides of existing structures.
• The extent of the smooth ER network depends on the actin
and microtubule cytoskeleton of the cell.
Function of Smooth Endoplasmic Reticulum
• The dynamic nature of the smooth endoplasmic reticulum is particularly
important in the liver that detoxifies a number of substances and makes them easy
to remove from the body.
• The smooth ER is important in the synthesis of lipids, such as cholesterol and
phospholipids, which form all the membranes of the organism.
• In addition it is important for the synthesis and secretion of steroid hormones
from cholesterol and other lipid precursors.
• In addition, it is involved in carbohydrate metabolism. For instance, the final
reaction of gluconeogenesis occurs in the lumen of the smooth ER since it contains
the enzyme glucose-6-phosphatase. This enzyme catalyzes the production of
glucose from glucose-6-phosphate.
• In muscle cells, a specialized SER called the sarcoplasmic reticulum is responsible
for storage of the calcium ions that are needed to trigger the coordinated
contractions of the muscle cells.
How ER contributes to Endomembrane system?
Protein processing-
• The proximity of the rough ER to the cell nucleus gives the ER unique control over
protein processing.
• Protein synthesis begins in the cytosol with a process known as translation, in which the
protein is assembled from an RNA sequence.
• The ribosomes on rough ER specialize in the synthesis of proteins that possess a signal
sequence that directs them specifically to the ER for processing.
• Note-A number of other proteins in a cell, including those destined for the nucleus
and mitochondria, are targeted for synthesis on free ribosomes, or those not attached to
the ER membrane.
• The signal sequence stops translation and directs the ribosomes — which are carrying
the unfinished proteins — to dock with ER proteins before finishing their work.
• As the protein grows, if it contains a signal sequence at its
amino-terminal end, it will become bound to a signal
recognition particle, which carries the ribosome to the
RER membrane.
• Once bound to the RER, the signal recognition particle
dissociates, when bound to SRP receptor present on the
ER membrane and protein translation continues.
• The newly formed protein then either becomes
embedded in the RER membrane, in the case of a
transmembrane protein, or is transmitted into the RER
lumen via a translocon channel, in the case of a water-
soluble protein.
• The signal peptidase (SPase) enzyme is responsible for
cleavage of the signal peptide from the preprotein,
allowing release from the membrane and correct folding
of the mature protein.
Protein modification
• The ER lumen plays four major protein processing roles: folding/refolding of the polypeptide,
glycosylation of the protein, assembly of multi-subunit proteins, and packaging of proteins into
vesicles.
• Refolding of proteins is an important process because the initial folding patterns as the
polypeptide is still being translated and unfinished may not be the optimal folding pattern once
the entire protein is available.
• Glycosylation is an important modification to eukaryotic proteins because the added sugar
residues are often used as molecular flags or recognition signals to other cells than come in
contact with them. There are two types of protein glycosylation, both of which require import
of the target polypeptide into the ER. N-linked glycosylation actually begins in the endoplasmic
reticulum, but O-linked glycosylation does not occur until the polypeptide has been transported
into the Golgi apparatus.
• The process of N-linked glycosylation
starts with the formation of dolichol-
linked GlcNAc sugar.
• Dolichol is a lipid molecule composed of
repeating isoprene units. This molecule is
found attached to the membrane of the
ER.
• Sugar molecules are attached to the
dolichol through a pyrophosphate
linkage (one phosphate was originally
linked to dolichol, and the second
phosphate came from
the nucleotide sugar).
• The oligosaccharide chain is then
extended through the addition of various
sugar molecules in a stepwise manner to
form a precursor oligosaccharide
Protein transport-
• The membrane lipids and proteins that are synthesized in the ER must be transported
through the network to their final destination in membrane-bound vesicles.
• The proteins that are synthesized in the ER have, as part of their amino acid sequence, a
signal that directs them where to go, much like an address directs a letter to its destination.
• Entry of a nascent protein into the secretory pathway is initiated by the selective
incorporation of correctly folded and assembled secretory and membrane proteins into
vesicles formed by the cytoplasmic COPII coat.
• Assembly of COPII coat proteins occurs at membrane regions known as ER exit sites.
• Proteins are carried from the ER to the Golgi by vesicles (transitional vesicles). These
vesicles bud from the ER cisternae through the COPII.
• Proteins that are normally exported from the E R must be properly folded. Abnormally
proteins are retained by chaperone molecules
THE GOLGI APPARATUS
• Before reaching their final destination, the lipids or proteins within the transport vesicles
still need to be sorted, packaged, and tagged so that they wind up in the right place.
• Golgi is membrane-bound organelle of eukaryotic cells that is made up of a series of
flattened, stacked pouches called cisternae.
• The Golgi apparatus itself is structurally polarized, with three primary compartments lying
between the “cis” face and the “trans” face. These faces are biochemically distinct, and the
enzymatic content of each segment is markedly different.
• The cisternae are held together by matrix proteins, and the whole of the Golgi apparatus is
supported by cytoplasmic microtubules.
• The three primary compartments of the apparatus are known generally as “cis” (cisternae
nearest the endoplasmic reticulum), “medial” (central layers of cisternae), and “trans”
(cisternae farthest from the endoplasmic reticulum). Two networks, the cis Golgi network
and the trans Golgi network, which are made up of the outermost cisternae at the cis and
trans faces, are responsible for the essential task of sorting proteins and lipids that are
received (at the cis face) or released (at the trans face) by the organelle.
How does Golgi contributes to Endomembrane system?
Protein trafficking____
• Transport vesicles from the ER travel to the cis face, fuse with it,
and empty their contents into the lumen of the Golgi apparatus.
• When a vesicle cluster fuses with the cis membrane, the
contents are delivered into the lumen of the cis face cisterna.
• As proteins and lipids progress from the cis face to the trans
face, they are modified into functional molecules and are
marked for delivery to specific intracellular or extracellular
locations.
• Finally, the modified and tagged proteins are packaged into
secretory vesicles that bud from the trans face of the Golgi. While
some of these vesicles deposit their contents into other parts of
the cell where they will be used, other secretory vesicles fuse
with the plasma membrane and release their contents outside the
cell.
• COPI coat proteins are used between parts of the Golgi apparatus
as well as to form vesicles going from the Golgi back to the ER.
Finally, clathrin is used to form vesicles leaving the Golgi for the
plasma membrane as well as for vesicles formed from the plasma
membrane for endocytosis.
Protein modification___
• Protein modifications involve cleavage of oligosaccharide side chains followed by
attachment of different sugar moieties in place of the side chain.
• Other modifications may involve the addition of fatty acids or phosphate groups
(phosphorylation) or the removal of monosaccharides.
• The different enzyme-driven modification reactions are specific to the compartments
of the Golgi apparatus. For example, the removal of mannose moieties occurs
primarily in the cis and medial cisternae, whereas the addition
of galactose or sulfate occurs primarily in the trans cisternae.
• In the final stage of transport through the Golgi apparatus, modified proteins and
lipids are sorted in the trans Golgi network and are packaged into vesicles at the
trans face. These vesicles then deliver the molecules to their target destinations, such
as lysosomes or the cell membrane.
• O-linked glycolysis
• O-glycosylation is a post-translational modification that
occurs after the protein has been synthesized.
• O-linked glycosylation is the attachment of
a sugar molecule to the oxygen atom of serine (Ser)
or threonine (Thr) residues in a protein.
• O-linked glycoproteins begin their glycosylation with the
action of the Golgi-specific enzyme, GalNAc transferase,
which attaches an N-acetylgalactosamine to the hydroxyl
group of a serine or threonine.
• The determination of which residue to glycosylate appears
to be directed by secondary and tertiary structure of the
protein.
In another example of form following function, cells that engage in a great deal of secretory activity (such as cells of the salivary
glands that secrete digestive enzymes or cells of the immune system that secrete antibodies) have an abundance of Golgi.
In plant cells, the Golgi apparatus has the additional role of synthesizing polysaccharides, some of which are incorporated into the
cell wall and some of which are used in other parts of the cell.
LYSOSOMES
• Lysosomes are sphere-shaped sacs filled with hydrolytic enzymes that have the
capability to break down many types of biomolecules.
• Lysosomes are membrane-bound organelles and the area within the membrane is
called the lumen, which contains the hydrolytic enzymes and other cellular debris.
• The pH level of the lumen lies between 4.5 and 5.0, which makes it quite acidic. It is
almost comparable to the function of acids found in the stomach.
• Inside the membrane, the organelle contains enzymes in the crystalline form.
• Lysosomal Enzymes
Proteases, which digest proteins
Lipases, which digests lipids
Amylase, which digests carbohydrates
Nucleases, which digest nucleic acids
Phosphoric acid monoesters
How lysosomes contribute to Endomembrane System?
• Lysosomes are usually meeting-places where several streams of
intracellular traffic converge. Digestive enzymes are delivered to them by
a route that leads outward from the ER via the Golgi apparatus, while
substances to be digested are fed in by at least three paths, depending on
their source.
• Both lysosomal hydrolases and membrane proteins are synthesized in
the rough ER and transported through the Golgi apparatus to
the trans Golgi network. The transport vesicles that deliver these proteins
to late endosomes (which later form lysosomes) bud from the trans Golgi
network.
• The vesicles incorporate the lysosomal proteins and exclude the many
other proteins being packaged into different transport vesicles for
delivery elsewhere.
How are lysosomal proteins recognized and selected in the trans Golgi
network with the required accuracy?
• For the lysosomal hydrolases the answer is known. They carry a unique
marker in the form of mannose 6-phosphate (M6P) groups, which are
added exclusively to the N-linked oligosaccharides of these soluble
lysosomal enzymes as they pass through the lumen of the cis Golgi
network .
• The M6P groups are recognized by
transmembrane M6P receptor proteins, which are present in
the trans Golgi network.
• The receptor proteins bind to lysosomal hydrolases on the lumenal side
of the membrane and to adaptins in assembling clathrin coats on the
cytosolic side.
• In this way, they help package the hydrolases into clathrin-coated vesicles
that bud from the trans Golgi network. The vesicles subsequently deliver
their contents to a late endosome.
• The clathrin-coated vesicles produced bud off from the trans Golgi network and fuse with
late endosomes.
• At the low pH of the late endosome, the hydrolases dissociate from the M6P receptors, and
the empty receptors are recycled to the Golgi apparatus for further rounds of transport
• . It is not known which type of coat mediates vesicle budding in the M6P receptor recycling
pathway.
• In the late endosomes, the phosphate is removed from the mannose sugars attached to the
hydrolases, further ensuring that the hydrolases do not return to the Golgi apparatus with
the receptor.
Vesicles
• Vesicles are small membrane-enclosed
transport units that can transfer
molecules between different
compartments. Most vesicles transfer
the membranes assembled in the
endoplasmic reticulum to the Golgi
apparatus, and then from the Golgi
apparatus to various locations
• There are three well known types of
vesicles. They are clathrin-coated, COPI-
coated, and COPII-coated vesicles. Each
performs different functions in the cell.
For example, clathrin-coated vesicles
transport substances between the Golgi
apparatus and the plasma membrane.
COPI- and COPII-coated vesicles are
frequently used for transportation
between the ER and the Golgi
apparatus.
Conclusion
• The endomembrane system of eukaryotic cells consists of the ER, the
Golgi apparatus, and lysosomes. Membrane components, including
proteins and lipids, are exchanged among these organelles and the plasma
membrane via vesicular transport with the help of molecular tags that
direct specific components to their proper destinations.
• The organelles of the endomembrane system are related through direct
contact or by the transfer of membrane segments as vesicles. Despite
these relationships, the various membranes are not identical in structure
and function.
• The system is defined more accurately as the set of membranes that form
a single functional and developmental unit, either being connected
directly, or exchanging material through vesicle transport
References
1. Lodish H, et al. (2000). "Section 5.4 Organelles of the
Eukaryotic Cell". Molecular Cell Biology. W. H. Freeman and
Company. Retrieved 2008-12-09.
2. Cooper G (2000). "The Mechanism of Vesicular
Transport". The Cell: A Molecular Approach. Sinauer
Associates, Inc. Retrieved 2008-12-09.
3. Futerman AH (December 2006). "Intracellular trafficking
of sphingolipids: relationship to biosynthesis". Biochimica et
Biophysica Acta (BBA) - Biomembranes.
Thank you
