Organelles Part 1 PDF

Ribosomes Endoplasmic Reticulum Golgi Apparatus Ribosomes: Structure Ribosomes are non-membranous organelles that consist of a small (40S) and a large (60S )subunit. The two subunits are composed of several types of ribosomal ribonucleic acids (rRNAs) and numerous proteins. Ribosomes co...

Ribosomes Endoplasmic Reticulum Golgi Apparatus Ribosomes: Structure Ribosomes are non-membranous organelles that consist of a small (40S) and a large (60S )subunit. The two subunits are composed of several types of ribosomal ribonucleic acids (rRNAs) and numerous proteins. Ribosomes constitute a single interchangeable population whether they are (1) located free in the cytosol; (2) bound to membranes of the rough endoplasmic reticulum (RER); and (3) attached to the cytoplasmic surface of the outer nuclear membrane. A polyribosome (polysome) is a cluster of ribosomes along a single strand of messenger ribonucleic acid (mRNA) where every ribosome is concurrently engaged in protein synthesis. Ribosomes These ribosomal proteins are themselves synthesized in cytoplasmic ribosomes, but are then imported to the nucleus where they associate with newly synthesized rRNA. The ribosomal subunits thus formed then move from the nucleus to the cytoplasm where they are reused many times, for translation of any mRNA strand. In stained preparations of cells, polyribosomes are intensely basophilic because of the numerous phosphate groups of the constituent RNA molecules that act as polyanions. Thus, cytoplasmic regions that stain intensely with hematoxylin and basic dyes, such as methylene and toluidine blue, indicate sites of active protein synthesis. Ribosomes: Function Ribosomes are organelles on which mRNA is translated into protein. Proteins destined for transport (secretory, membrane, and lysosomal) are synthesized on polyribosomes bound to the RER, whereas proteins destined to remain in the cytosol are synthesized on polyribosomes in the cytosol. Cytosolic protein synthesis: The small ribosomal subunit binds both mRNA and activated transfer ribonucleic acids (tRNAs ); the codons of the mRNA then base-pair with the corresponding anticodons of the tRNAs. Ribosomes: Function Next, an initiator tRNA recognizes the start codon (AUG) on the mRNA. The large ribosomal subunit then binds to the complex. The enzyme peptidyl transferase located in the large subunit catalyzes peptide bond formation, resulting in addition of amino acids to the growing polypeptide chain. A chain-termination (stop) codon (UAA, UAG, or UGA) causes release of the polypeptide from the ribosome, and the ribosomal subunits dissociate from the mRNA. Proper folding of new proteins is guided by protein chaperones. Denatured proteins or those that cannot be refolded properly are conjugated to the protein ubiquitin that targets them for breakdown by proteasomes Endoplasmic Reticulum (ER) The cytoplasm of most cells contains a convoluted membranous network called the endoplasmic reticulum (ER). This network (reticulum) extends from the surface of the nucleus throughout most of the cytoplasm and encloses a series of intercommunicating channels called cisternae. Numerous polyribosomes attached to the membrane in some regions of ER allow two types of ER to be distinguished: RER and SER. Rough Endoplasmic Reticulum (RER): Structure RER, as apparent in TEM, is a system of membrane-bounded sacs, or narrow tubules whose outer surface is studded with ribosomes, whose large subunit binds to proteins, called ribophorins, located in the outer RER membrane. The outer nuclear membrane is continuous with the RER; therefore, its lumen, the perinuclear cisterna, is confluent with the cisternae of the RER. RER is abundant in cells synthesizing secretory proteins such as pancreatic acinar cells (making digestive enzymes), fibroblasts (collagen), and plasma cells (immunoglobulins). The RER sac closest to the Golgi apparatus gives rise to buds free of ribosomes that form vesicles known as transfer vesicles. This sac is known as a transitional element and represents the region of exit from the RER. The presence of polyribosomes on the cytosolic surface of the RER confers basophilic staining properties on this organelle when viewed with the light microscope. Protein Synthesis on RER The major function of RER is production of membrane-associated proteins, proteins of many membranous organelles, and proteins to be secreted by exocytosis. Production here includes the initial (core) glycosylation of glycoproteins, certain other posttranslational modifications of newly formed polypeptides, and the assembly of multichain proteins. These activities are mediated by resident enzymes of the RER and by protein complexes that act as chaperones guiding the folding of nascent proteins, inhibiting aggregation, and generally monitoring protein quality within the ER. Protein synthesis begins on polyribosomes in the cytosol. The 5′ ends of mRNAs for proteins destined to be segregated in the ER encode an N-terminal signal sequence of 15-40 amino acids that includes a series of six or more hydrophobic residues. The newly translated signal sequence is bound by a protein complex called the signal- recognition particle (SRP), which inhibits further polypeptide elongation. Protein Synthesis on RER The SRP–ribosome–nascent peptide complex binds to SRP receptors on the ER membrane. SRP then releases the signal sequence, allowing translation to continue with the nascent polypeptide chain transferred to a translocator complex (also called a translocon) through the ER membrane. Inside the lumen of the RER, the signal sequence is removed by an enzyme, signal peptidase. With the ribosome docked at the ER surface, translation continues with the growing polypeptide pushing itself while chaperones and other proteins serve to “pull” the nascent polypeptide through the translocator complex. Upon release from the ribosome, posttranslational modifications and proper folding of the polypeptide continue.  RER has a highly regulated system to prevent nonfunctional proteins being forwarded to the pathway for secretion or to other organelles. New proteins that cannot be folded or assembled properly by chaperones undergo ER-associated degradation (ERAD), in which unsalvageable proteins are translocated back into the cytosol, conjugated to ubiquitin, and then degraded by proteasomes. Rough Endoplasmic Reticulum (RER): Function The RER is where proteins that are to be packaged are synthesized, including secretory, cell membrane, and lysosomal proteins. The RER monitors the assembly, retention, and even degradation of certain proteins. Proteins that are to be retained in the RER cisternae are marked by the presence of a small peptide at their C terminus, known as the KDEL sequence, composed of lysine, asparagine, glutamine, and leucine. Proteins that do not sport the KDEL sequence at the C terminus are transported out of the cisternae of the RER. Smooth Endoplasmic Reticulum (SER): Structure SER is an irregular network of membrane-bounded channels that lack ribosomes on its surface, which makes it appear smooth. Lacking polyribosomes, SER is not basophilic and is best seen with the TEM. Unlike the cisternae of RER, SER cisternae are more tubular or saclike, with interconnected channels of various shapes and sizes rather than stacks of flattened cisternae. SER is less common than RER but is prominent in cells synthesizing steroids, triglycerides, and phospholipids and cholesterol. Smooth Endoplasmic Reticulum (SER): Function SER has different functions in different cell types. Steroid hormone synthesis occurs in SER-rich cells such as the Leydig cells of the testis, which make testosterone. Fatty acid and phospholipid synthesizing cells are rich in SER. Drug detoxification occurs in hepatocytes (P450 system) following proliferation of the SER in response to the drug phenobarbital; the oxidases that metabolize this drug are located in the SER. Muscle contraction and relaxation involve the release and recapture of Ca2+ by the SER in skeletal muscle cells, called the sarcoplasmic reticulum. Golgi Apparatus (complex): Structure The Golgi apparatus consists of several membrane-bounded cisternae (saccules) arranged in a stack and positioned and held in place by microtubules. Cisternae are disk shaped and slightly curved, with flat centers and dilated rims, but their size and shapes vary. The morphology of these units is due to the presence of Golgi membrane- associated proteins; additionally, F-actins connect the cisternae to each other. A distinct polarity exists across the Golgi stack, with many vesicles present near the nucleus (the entry side into the Golgi apparatus) and larger secretory granules (vacuoles) away from the nucleus (the exit side of the Golgi apparatus). Golgi Apparatus (complex): Regions The cis face of the Golgi apparatus typically lies deep in the cell toward the nucleus next to the transitional element of the RER. Its outermost cistema is associated with a network of interconnected tubes and vesicles, called vesicular- tubular clusters (VTC; previously known as ERGIC), which receives transfer vesicles from the transitional element of the RER. The medial compartment of the Golgi apparatus is composed of several cisternae located between the cis and trans faces. The trans face of the Golgi apparatus lies at the side of the stack facing the cell membrane and is associated with vacuoles and secretory granules. The trans-Golgi network (TGN) lies apart from the last cisterna at the trans face and is separated from the Golgi stack. It sorts proteins for their final destinations. Golgi Apparatus: Transport Formation of transport vesicles and secretory vesicles is driven by assembly of various coat proteins (including clathrin), which also regulate vesicular traffic to, through, and beyond the Golgi apparatus. Forward movement of vesicles in the cis Golgi network of saccules is promoted by the coat protein COP-II, while retrograde movements in that region involve COP-I. Other membrane proteins important for directed vesicle fusion include various Rab proteins and other enzymes, receptors and specific binding proteins, and fusion- promoting proteins that organize and shape membranes. Depending on the activity of these proteins, vesicles are directed toward different Golgi regions and give rise to lysosomes or secretory vesicles for exocytosis. Golgi saccules at sequential locations contain different enzymes at different cis, medial, and trans levels. Golgi Apparatus (complex): Function Golgi apparatus, or Golgi complex, completes posttranslational modifications (glycosylation, sulfation, phosphorylation) and limited proteolysis of proteins produced in the RER and then packages and addresses these proteins to their proper destinations (storage, secretion). So, the Golgi apparatus synthesizes carbohydrates, processes membrane-packaged proteins synthesized in the RER, and also recycles and redistributes membranes.