Constitutive Secretion

r E. Protein coding in DNA and RNA

dna [taaaatgctctc]

Codogen

Transcription and Splicing Export from nucleus 5'

mRNA lAUUUUACGAGAG

Protein

NH2 Ij Ile Leu Arg

Growth of peptide chain o 'tÄ

TD u

plasmic reticulum (RER). These ribosomes synthesize export proteins as well as transmembrane proteins (^ G) for the plasma membrane, endoplasmic reticulum, Golgi apparatus, lysosomes, etc. The start of protein synthesis (at the amino end) by such ribosomes (still unattached) induces a signal sequence to which a signal recognition particle (SRP) in the cytosol attaches. As a result, (a) synthesis is temporarily halted and (b) the ribosome (mediated by the SRP and a SRP receptor) attaches to a ribosome receptor on the ER membrane. After that, synthesis continues. In export protein synthesis, a translocator protein conveys the peptide chain to the cisternal space once synthesis is completed. Synthesis of membrane proteins is interrupted several times (depending on the number of membrane-spanning domains (^ G2) by translocator protein closure, and the corresponding (hydrophobic) peptide sequence is pushed into the phospholipid membrane. The smooth endoplasmic reticulum (SER) contains no ribosomes and is the production site of lipids (e.g., for lipo-proteins, ^ p.254ff.) and other substances. The ER membrane containing the synthesized membrane proteins or export proteins forms vesicles which are transported to the Golgi apparatus.

The Golgi complex or Golgi apparatus (^ F) has sequentially linked functional compartments for further processing of products from the endoplasmic reticulum. It consists of a cis-Golgi network (entry side facing the ER), stacked flattened cisternae (Golgi stacks) and a trans-Golgi network (sorting and distribution). Functions of the Golgi complex: ! polysaccharide synthesis; ! protein processing (posttranslational modification), e.g., glycosylation of membrane proteins on certain amino acids (in part in the ER) that are later borne as glycocalyces on the external cell surface (see below) and -y-carboxy-lation of glutamate residues (^ p. 102 ); ! phosphorylation of sugars of glycoproteins (e.g., to mannose-6-phosphate, as described below);

! "packaging" of proteins meant for export into secretory vesicles (secretory granules), the contents of which are exocytosed into the extracellular space; see p. 246, for example.

Hence, the Golgi apparatus represents a central modification, sorting and distribution center for proteins and lipids received from the endoplasmic reticulum.

Regulation of gene expression takes place on the level of transcription C1a), RNA modification (^ C1b), mRNA export (^ C1c), RNA degradation (^ C1d), translation (^ C1e), modification and sorting (^ F,f), and protein degradation (^ F,g).

The mitochondria (^ A, B; p. 17 B) are the site of oxidation of carbohydrates and lipids to CO2 and H2O and associated O2 expenditure. The Krebs cycle (citric acid cycle), respiratory chain and related ATP synthesis also occur in mitochondria. Cells intensely active in metabolic and transport activities are rich in mito-chondria—e.g., hepatocytes, intestinal cells, and renal epithelial cells. Mitochondria are enclosed in a double membrane consisting of a smooth outer membrane and an inner membrane. The latter is deeply infolded, forming a series of projections (cristae); it also has important transport functions (^ p. 17 B). Mitochondria probably evolved as a result of symbiosis between aerobic bacteria and anaerobic cells (symbiosis hypothesis). The mitochondrial DNA (mtDNA) of bacterial origin and the double membrane of mitochondria are relicts of their ancient history. Mitochondria also contain ribosomes which synthesize all proteins encoded by mtDNA.

Lysosomes are vesicles (^ F) that arise from the ER (via the Golgi apparatus) and are involved in the intracellular digestion of macro-molecules. These are taken up into the cell either by endocytosis (e.g., uptake of albumin into the renal tubules; ^ p. 158) orby phagocytosis (e.g., uptake of bacteria by macrophages; ^ p.94ff.). They may also originate from the degradation of a cell's own organelles (auto-phagia, e.g., of mitochondria) delivered inside autophagosomes (^ B, F). A portion of the en-docytosed membrane material recycles (e.g., receptor recycling in receptor-mediated en-docytosis; ^ p. 28). Early and late endosomes are intermediate stages in this vesicular transport. Late endosomes and lysosomes contain acidic hydrolases (proteases, nucleases, li-pases, glycosidases, phosphatases, etc., that are active only under acidic conditions). The

F. Protein synthesis, sorting, recycling, and breakdown

Nucleus

Cytosol

F. Protein synthesis, sorting, recycling, and breakdown

Nucleus

Cytosol

Protein Transport After Synthesis
Cytosolic proteins

Protein and lipid synthesis

Mitochondrion

Endoplasmatic reticulum (ER)

Mitochondrion

Endoplasmatic reticulum (ER)

Constitutive Secretion

Constitutive secretion

Controlled protein secretion

Constitutive secretion

Controlled protein secretion o 'tÄ

TD u

membrane contains an H+-ATPase that creates an acidic (pH 5) interior environment within the lysosomes and assorted transport proteins that (a) release the products of digestion (e.g., amino acids) into the cytoplasm and (b) ensure charge compensation during H+ uptake (Cl-channels). These enzymes and transport proteins are delivered in primary lysosomes from the Golgi apparatus. Mannose-6-phosphate (M6 P) serves as the "label" for this process; it binds to M6 P receptors in the Golgi membrane which, as in the case of receptor-mediated en-docytosis (^ p. 28), cluster in the membrane with the help of a clathrin framework. In the acidic environment of the lysosomes, the enzymes and transport proteins are separated from the receptor, and M6 P is dephosphory-lated. The M6 P receptor returns to the Golgi apparatus (recycling, ^ F). The M6 P receptor no longer recognizes the dephosphorylated proteins, which prevents them from returning to the Golgi apparatus.

Peroxisomes are microbodies containing enzymes (imported via a signal sequence) that permit the oxidation of certain organic molecules (R-H2), such as amino acids and fatty acids: R-H2 + O2 ^ R + H2O2. The peroxi-somes also contain catalase, which transforms 2 H2O2 into O2 + H2O and oxidizes toxins, such as alcohol and other substances.

Whereas the membrane of organelles is responsible for intracellular compartmentaliza-tion, the main job of the cell membrane (^ G) is to separate the cell interior from the extracellular space (^ p. 2). The cell membrane is a phospholipid bilayer (^ G1) that may be either smooth or deeply infolded, like the brush border or the basal labyrinth (^ B). Depending on the cell type, the cell membrane contains variable amounts of phospholipids, cholesterol, and glycolipids (e.g., cerebrosides). The phos-pholipids mainly consist of phosphatidylcho-line (^ G3), phosphatidylserine, phosphati-dylethanolamine, and sphingomyelin. The hy-drophobic components of the membrane face each other, whereas the hydrophilic components face the watery surroundings, that is, the extracellular fluid or cytosol (^ G4). The lipid composition of the two layers of the membrane differs greatly. Glycolipids are present only in the external layer, as described below. Cholesterol (present in both layers) reduces both the fluidity of the membrane and its permeability to polar substances. Within the two-dimensionally fluid phospholipid membrane are proteins that make up 25% (myelin membrane) to 75% (inner mitochondrial membrane) of the membrane mass, depending on the membrane type. Many of them span the entire lipid bilayer once (^ G1) or several times (^ G2) (transmembrane proteins), thereby serving as ion channels, carrier proteins, hormone receptors, etc. The proteins are anchored by their lipophilic amino acid residues, or attached to already anchored proteins. Some proteins can move about freely within the membrane, whereas others, like the anion exchanger of red cells, are anchored to the cy-toskeleton. The cell surface is largely covered by the glycocalyx, which consists of sugar moieties of glycoproteins and glycolipids in the cell membrane (^ G1,4) and of the extracellular matrix. The glycocalyx mediates cell-cell interactions (surface recognition, cell docking, etc.). For example, components of the glycocalyx of neutrophils dock onto en-dothelial membrane proteins, called selectins (^ p. 94).

The cytoskeleton allows the cell to maintain and change its shape (during cell division, etc.), make selective movements (migration, cilia), and conduct intracellular transport activities (vesicle, mitosis). It contains actin filaments as well as microtubules and intermediate filaments (e.g., vimentin and desmin filaments, neurofilaments, keratin filaments) that extend from the centrosome.

Lipid molecule

Integral membrane protein Glycoprotein

Glycolipid

- Extracellular

Lipid molecule

Cytotoxicedema

— Glycocalyx

Lipid bilayer (ca. 5 nm)

1 Membrane constituents

2 Multiple membrane-spanning Integral protein

— Glycocalyx

2 Multiple membrane-spanning Integral protein

3 Phospholipid (phosphatidylcholine)

Lipid bilayer (ca. 5 nm)

Cytosol

Peripheral membrane protein

1 Membrane constituents

Glycolipid

Cholesterol

Was this article helpful?

0 0
Reducing Blood Pressure Naturally

Reducing Blood Pressure Naturally

Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

Get My Free Ebook


Responses

  • raino
    What is the difference between integral protein, peripheral protein, and a transmembrain protein?
    8 years ago

Post a comment