Endomembrane system Endomembrane System Outer Nuclear envelope Direct physical continuity Transfer of membrane segments as vesicles Endoplasmic reticulum BUT membranes are not identical in structure and function Golgi apparatus Lysosomes Peroxisomes Vesicles Plasma membrane 1
Organelle Structure: The Endoplasmic Reticulum The endoplasmic reticulum contains a network of branching and joining tubules 400 to 700 angstroms in diameter and flattened sacs extending throughout the cytosol. It has been calculated that 1ml of liver tissue contains about 11 square meters of endoplasmic reticulum. The encircling membranes are about 50 to 60 angstroms thick and have the same substructure as the plasma membrane The ER is continuous with the nuclear membrane 2
The Endoplasmic Reticulum The tubules and sacs interconnect enclosing a single internal space known as the ER cisternal space or ER lumen ER membrane separates cisternal space from the cytosol and mediates selective transfer of proteins from cytosol into the ER. The ER is the site of production of all transmembrane proteins and lipids for most of the cellular organelles: (ER, Golgi apparatus, lyosomes, secretory vesicles and plasma membrane) There are two types of Endoplasmic Reticulum: Rough ER Smooth ER 3
Rough Endoplasmic Reticulum (rer) Cytosolic surface has ribosomes bound to it that are synthesizing protein. Rough ER thus participates in protein synthesis and, in the process, incorporates proteins into the ER membrane. Rough Endoplasmic Reticulum (rer) The proteins captured by the ER are of two types Transmembrane proteins, which are only partly translocated across the ER membrane as they are being synthesized and become imbedded in it. Water-soluble proteins, which are fully translocated across the ER membrane as they are synthesized and released into the ER lumen 4
Import of a protein destined for the LUMEN of the ER and possibly further translocation. Signal peptidase on inner surface of ER membrane cleaves off the amino end (and the initiator methionine) of the imported protein. The need for stop transfer signal sequence in proteins which have to remain integral inside the membrane. Proteins which span the membrane SEVERAL TIMES, need several of these start and stop transfer sequences 5
Rough Endoplasmic Reticulum (rer) Some of the transmembrane proteins function in the ER and many others are destined for the plasma membrane or the membranes of other organelles. The water-soluble proteins are destined for the lumen of an organelle or for secretion. All of these proteins are directed to the ER membrane by the same signal sequence and are translocated across it by similar mechanisms. RER functions Protein Synthesis 6
Polypeptide is moved from the translocon to the cisterna Enzymes in the membrane Signal peptide removed signal peptidase Carbohydrates added oligosaccharyltransferase Topic 4 RER and Golgi add sugars to proteins to make glycoproteins. 7
RER functions Processing of proteins In the lumen Chaperones BiP (binding protein)» Recognize and bind unfolded proteins» Aid in achieving native conformation» Movement of the protein into the ER lumen» Protein disulfide isomerase (PDI) Topic 4 Misfolded proteins 1. Transported to cytosol 2. Destroyed in proteasomes 8
Rough Endoplasmic Reticulum Cells that specialize in secreting proteins have lots of rough ER Rough Endoplasmic Reticulum nucleus nuclear envelope endoplasmic reticulum 1 m 9
Smooth Endoplasmic Reticulum (ser) Regions of ER that lack ribosomes are called smooth ER Functions: Contain ER exit sites from which transport vesicles carrying newly synthesized lipids and proteins bud off on route to the Gogi apparatus Smooth Endoplasmic Reticulum (ser) Functions: Site for synthesis and metabolism of lipids Fatty acids, phospholipids, steroids Steroid production Seen in cells of adrenal gland, gonads Formed with cholesterol : Estrogen, testosterone, cortisol, progesterone Glycogen breakdown In liver cells, presence of G-6-P Store calcium ions in muscle tissue In muscle cells, regulates contraction called the sarcoplasmic reticulum ser involved in esterification of vitamin A ( Rhodopsin, the visual pigment) Contain enzymes that detoxify lipid-soluble drugs Carried out by cytochrome P 450 This is a family of eznymes that hydroxylate lipid-soluble drugs This makes them water-soluble so they can be secreted (e.g. Insecticides) 10
Retinal Pigment Cell 11
Endoplasmic reticulum 1 ml of liver tissue contains about 11 square meters of endoplasmic reticulum 12
Smooth endoplasmic reticulum Rough endoplasmic reticulum The Endomembrane System RER vs SER RER ribosomes bound to cytosolic surface Interconnected sacs cisternae Continuous with nuclear envelope SER No ribosomes Tubular Interconnecting pipelines 13