CELLULAR MEMBRANES

Endomembrane Structure Endoplasmic Reticulum (smooth) Endoplasmic Reticulum (rough) Golgi Plasma membrane Lysosomes % total membrane in Hepatocyte 16 35 7 2 0.4 % total in Pancreatic Exocrine Cell <1 60 10 5 N.D.

Peroxisomes
Endosomes Mitochondria Nuclear envelope (inner only)

0.4
0.4 39 0.2

N.D.
N.D. 21 0.7

ORIGIN OF ER

The nucleus and endoplasmic reticulum arose from infoldings of prokaryotic cell membrane

Endoplasm is the inner part of a cell's cytoplasm and Reticulum means a fine network.

Endoplasmic reticulum is an interlinked network of cisternae (membrane disks), vesicles (intracellular transport sacs) and tubules inside a eukaryotic cell.

The endoplasmic reticulum was first observed by Ernest Fullam, Keith Porter and Albert Claude, in the year 1945.

 This network of tubules, vesicles and cisternae, is held together by the cell's cytoskeleton. This cytoskeleton is the cell's skeleton, made of proteins and embedded in cytoplasm.

The cisterns that constitute a major part of endoplasmic reticulum are sheathed in a phospholipids membrane, that separates it from the cytosol, which is the inner liquid inside a cell.
The whole network that constitutes the endoplasmic reticulum is made up of this one continuous phospholipid membrane and the whole network has a complex internal space or lumen. This space is called endoplasmic reticulum cisternal space.

 ER membranes are continuous can be proved by using fluorescently labeled protein and lipid.

Diffusion of these proteins and lipid from one type of ER into other indicates that their membranes are continuous. 3,3'-dihexyloxacarbocyanine iodide (also known as DiOC6(3)) is a lipophilic dye that vitally stains the ER network in living cells (such as this 3T3 cell).

 Present in all eukaryotic cell except egg cell, embryonic cell, matured mammalian RBC etc

Absent in prokaryotes All eukaryotic cells have an ER, more than half the total membrane

ER lumen or ER cisternal: one continuous space10% of the total cell volume

 The bilipid membrane controls the transport of molecules between cytoplasm and lumen. It's like a molecular pipeline, which connects the nucleus with cytoplasm.

This network transports molecules inside the cell, as well as outside.

There are two types of proteins that are found in the endoplasmic reticulum. They are the ones that are transported through it and the resident proteins, that are required for the functioning of the reticulum.

MOLECULAR PIPELINE

 The endoplasmic reticulum is made out of a lipid membrane(bimembrane str) The endoplasmic reticulum is still connected to the nuclear membrane that is wrap around the cells DNA.

There is a straight connection between the cells nucleus and the endoplasmic reticulum.

ER consists of following structure 1.Cisternae- Flattened sac like membrane bounded structure unbranched

3.Tubule-Membrane bounded branched tubular structure forming reticular system along with cisternae and vesicles 2.Vesicle- Droplet like membrane bounded structure at the end of tubule

 There are three types of endoplasmic reticulum, which are:

1.Rough Endoplasmic Reticulum (RER) 2.Smooth Endoplasmic Reticulum (SER) 3.Sarcoplasmic Reticulum (SR)

 One interesting feature of the endoplasmic reticulum is that the rough and smooth endoplasmic reticulum can transform from one type to another
Their transformation is subject to the needs of the cell and especially the enzymatic needs.

The transformation happens through the embedding of proteins.

The RER is dotted with ribosomes. (Which is why it is called rough.) The RER is involved with protein production, protein folding, quality control and dispatch.

Consists of network-like tunnels with tubules, vesicles and cisternae which is held together by the cytoskeleton of the cell. Rough endoplasmic reticulum is connected with the outer envelope of the cell nucleus.

Protein Generation
Production and processing of specific proteins at ribosomal sites that are later exported. The ribosome do their job and create proteins, which are then sent into the rough endoplasmic reticulum, for advanced processing. The amino acids and complex molecules needed for the job, are transported from the cytoplasm. The functioning of the reticulum involves creation of two types of proteins. One is the type which fortifies and gets embedded into the reticulum membrane. The other types are water soluble, which, after creation at ribosomal sites, pass through the membrane and into the lumen.

Protein Folding
The proteins that enter are further processed inside. Just like a two dimensional cardboard box is folded to make a box, the proteins are folded into the right three dimensional shapes and carbohydrates may be added. Many compounds are connected to the protein chain assembled in the lumen, according to requirement. Once the folding is complete, they are ready for delivery. The folding is made possible by chaperone proteins present in the lumen. Molecules like haemoglobin are produced in the rough endoplasmic reticulum.

Protein Transport Another RER function is to transport these ready proteins to the sites where they are required. They may also be sent to the Golgi bodies for further advanced processing, through vesicles.

PROTEIN TRANSPORT

Protein Quality Check After assembly, every protein created in the RER lumen is subjected to a thorough quality evaluation. The protein is checked for correct ordering and structure and if it doesn't match the exact requirement, it's simply rejected, stored in the lumen and sent back for recycling. Many medical conditions like Emphysema and a type of Cystic Fibrosis is caused due to the rejection of a crucial protein by this RER quality check system.

 The main difference in the structure of RER and SER is that the rough endoplasmic reticulum contains ribosomes, while the smooth endoplasmic reticulum does not contain this cell organelle. The embedded ribosome in the rough endoplasmic reticulum give it a rough appearance. On the other hand, the smooth endoplasmic reticulum looks like a group of smooth tubules. An interesting fact about rough endoplasmic reticulum (RER) is that the ribosomes are not attached to it permanently. Instead, they attach to the surface of RER at the time of protein synthesis.
Another type of endoplasmic reticulum is sarcoplasmic reticulum, which is a type of smooth endoplasmic reticulum and can be found in smooth, as well as striated muscles.

SER

Electron micrograph of smooth ER of Leydig cell of testis (site of steroid hormone synthesis)

 Vary in different cell types More commonly, it is concerned with certain metabolic processes

It takes part in several metabolic processes, besides providing surface area for the action of the enzymes.
It also serves as storage space for several important enzymes. Among the various metabolic processes, it plays an important role in carbohydrate metabolism and synthesis of lipids and steroids.

 Drug detoxification, attachment of receptors on cell membrane proteins and packaging proteins for transportation are some other important functions of SER. Drug detoxification takes place in SER, which are found in liver cells. It regulates the transportation of proteins to their proper locations. The small vesicles of SER are responsible for transporting proteins to the new locations. The enzyme, glucose-6-phosphate found in it takes part in glucogenesis. It converts glucose-6-phosphate to glucose.

 Another significant function of SER is, to store calcium in the muscle cells, and this crucial function is carried out by the sarcoplasmic reticulum. This type of SER is also concerned with the release of calcium at the time of need such as, during muscle contraction. (sarcoplasmic reticulum)

DETOXIFICATION BY SER
Organ- Liver Enzyme involve- Oxygenase (oxygen transferring enzyme)- Non specific to substrate Oxidise many hydrophobic compound into hydrophilic Effect is not always positive, for example relatively harmless compound benzopyrene is converted into a carcinogen after the action of this enzyme of SER.

 RER is abundant cell,Fibrioblast,Cells of Goblet cell, Liver cell etc

inPancreatic endocrine gland,

SER is abundant in- Adipocyte of adipose tissue,Adrenocortical cell, Intestinal absorptive cell, Liver cell etc

Polypeptides produced at RER includes Secreted protein Integral membrane protein Soluble protein (for endomembrane system)

 Cytosolic (like enzyme of glycolysis and protein for cytoskeleton) Peripheral protein of cytosolic surface of membrane Protein that are transported to nucleus Protein to be incorporate into the peroxisome , chloroplast and mitochondria (in last two protein is transported after completion in cytosol)

 SIGNAL HYPOTHESIS
(Nobel Prize for Medicine - 1999) Nascent polypeptides possess N-terminal address code targets ribosome complex to ER membrane

Synthesis of SECRETED PROTEIN on ER membrane-bound ribosome

Binding immunoglobulin protein (BiP) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5(HSPA5) is a HSP70 molecular chaperone

It is located in the lumen of the endoplasmic reticulum that binds newly-synthesized proteins as they are translocated into the ER, and maintains them in a state competent for subsequent folding and oligomerization.

Synthesis of INTEGRAL MEMBRANE PROTEIN on ER-bound ribosome

 Considering the various rough and smooth endoplasmic reticulum roles, it can be concluded that endoplasmic reticulum is one of the crucial cell organelle. Their existence is so important for vital life processes like, protein synthesis, carbohydrate metabolism, detoxification and lipid synthesis.

Golgi Apparatus

Introduction
The name comes from Italian anatomist Camillo Golgi, who identified it in 1898. Factory for packaging proteins and consists of stacks of flattened membranous sacs that may be distended in certain regions because they are filled with cell products.

Structure
The Golgi apparatus has a structure that is made up of cisternae, which are flattened stacks of membrane usually found in a series of five to eight. These cisternae help proteins travel from different points in the cell using enzyme The face of golgibody towards the nucleus is called as cis face and towards the plasma membrane is called as trans face

Structure.

The Golgi apparatus consists of stacks of sacs with vesicles pinching off from the edges of the sacs.

 Once the proteins are produced by the rough E.R. they pass into the sack like cisternae that are the main part of the golgi body. These proteins are then squeezed off into the little blebs which drift off into the cytoplasm.

Function
The golgi complex processes, sorts, modifies, and packages proteins. Proteins that pass through the golgi are: secreted from the cell plasma membrane proteins and proteins routed to other intracellular organelles pass through the golgi.

 Storage and packaging of materials that will be exported from the cell. The Golgi apparatus is often called the "shipping department" of the cell.

 The vesicles that pinch off from the Golgi apparatus move to the cell membrane and the material in the vesicle is released to the outside of the cell. Some of these pinched off vesicles also become lysosomes

Along with protein modification, Golgi apparatus is involved in the transport of lipids around the cell,

Protein transport
From the ER they are transported to the Golgi complex in small membrane-bound vesicles formed from the ER membrane. These vesicles then fuse with the membranes of the Golgi complex. The proteins then pass through the separate layers of the Golgi complex moving by way of membrane transport vesicles. During their passage- proteins are modified in different ways Carbohydrates are often added here or previously added carbohydrates are modified. In some cases, the carbohydrates and other modifications act as "sorting signals" allowing the GOLGI to route the protein to different parts of the cell.

Portion of the golgi closest to the plasma membrane and serves as the site where membrane-bound vesicles bud and then exit the golgi complex.

Is the site where membrane-bound vesicles from the ER first fuse.

Transport from the Golgi apparatus