Secretory proteins

Chaperones. Figure 2 The multiple roles of BiP in the biogenesis of the secretory proteins. BiP, immunoglobulin heavy chain binding protein ER, endoplasmic reticulum ERAD, ER-associated degradation ERj, resident ER protein with J-domain Sec61, core subunit of the protein translocase UPR, unfolded protein response that involves several signal transduction pathways that are activated in order to increase the biosynthetic capacity and decrease the biosynthetic burden of the ER... 

A system of membrane enclosed cisternae in the cytoplasm. The ER is continuous with the outer membrane of the nuclear envelope. The part of the ER coated with ribosomes is called rough ER, the other part is called smooth-surfaced ER. The rough ER is the first compartment of the secretory pathway. Here, membrane proteins are integrated into and secretory proteins translocated across the ER membrane. Furthermore,... 

Specific proteases located on the luminal side of the endoplasmic reticulum. They cleave the amino-terminal peptides from the precursor forms of membrane and secretory proteins. 

The signal recognition particle (SRP) is a cytosolic ribonucleoprotein complex which binds to signal sequences of nascent membrane and secretory proteins emerging from ribosomes. The SRP consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72 kD). It induces an elongation arrest until the nascent chain/ ribosome/SRP complex reaches the translocon at the endoplasmic reticulum (ER) membrane. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Secretory proteins and proteins destined for membranes distal to the ER completely traverse the membrane bilayer and are discharged into the lumen of the ER. 7V-Glycan chains, if present, are added (Chapter 47) as these proteins traverse the irmer part of the ER membrane—a process called cotranslational glycosyla-tion. Subsequently, the proteins are found in the... 

Figure 46-5 shows a variety of ways in which proteins are distributed in the plasma membrane, in particular, the amino terminals of certain proteins (eg, the LDL receptor) can be seen to be on the extracytoplasmic face, whereas for other proteins (eg, the asialoglycoprotein receptor) the carboxyl terminals are on this face. To explain these dispositions, one must consider the initial biosynthetic events at the ER membrane. The LDL receptor enters the ER membrane in a manner analogous to a secretory protein (Figure 46-4) it partly traverses... 

Kirkpatrick RB, Matico RE, McNulty DE, Strickler JE, Rosenberg M 1995 An abundantly secreted glycoprotein from Drosophila melanogaster is related to mammalian secretory proteins produced in rheumatoid tissues and by activated macrophages. Gene 153 147-154 Leconte I, Carpentier JL, Clauser E 1994 The functions of the human insulin receptor are affected in different ways by mutation of each of the four N-glycosylation sites in the fl subunit. J Biol Chem 269 18062-18071... 

Irikura, D., et at. (2007). Characterization of a major secretory protein in the cane toad (Bufo marinus) choroid plexus as an amphibian lipocalin-type prostaglandin D synthase. J. Biochem. 141, 173-80. 

Lippincott-Schwartz J, Roberts TH, Hirschberg K (2000) Secretory protein trafficking and organelle dynamics in living cells. Annu Rev Cell Dev Biol 16 557-589... 

Walter, P., and Blobel, G. (1981b). Translocation of proteins across the endoplasmic reticulum. II. Signal recognition protein (SRP) mediates the selective binding to microsomal membranes of in cdro-assembled polysomes synthesizing secretory protein. J. Cell Biol. 91, 551-556. 

DMP also has been used to study the interaction between the endoplasmic reticulum and microtubules (Ogawa-Goto et al., 2007), the conformational changes in the outer arm dynein of Chlamydomonas in response to calcium (Sakato et al., 2007), and the secretion of the adipocyte-specific secretory protein adiponectin (Wang et al., 2007). 

Wang, Z.V., Schraw, T.D., Kim, J.-Y., Khan, T., Rajala, M.W., Follenzi, A., and Scherer, P.E. (2007) Secretion of the adipocyte-specific secretory protein adiponectin critically depends on thiol-mediated protein retention. Mol. Cell. Biol. 27, 3716-3731. 

Processing of proteins in the Golgi complex includes sorting and glycosylation of membrane proteins and secretory proteins 148 Proteins and lipids move through Golgi cisternae from the cis to the trans direction 148... 

Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport 488... 

Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport. However, not all membrane-bounded organelles (MBOs) are destined for the axon. As a result, the first stage of transport must be synthesis, sorting and packaging of organelles (see Ch. 9). Once assembled, the organelle must then be committed to the transport... 

Passage through the Golgi apparatus is obligatory for most proteins destined for fast transport. In all cell types, secretory and integral membrane proteins are synthesized on polysomes bound to the endoplasmic reticulum. Secretory proteins enter the lumen of the reticulum, whereas membrane proteins become oriented within the... 

Transport of MBOs to their various destinations is typically mediated by MTs and motor molecules. Membrane and secretory proteins become associated with membranes either during or immediately following their synthesis, and then maintain this association throughout their lifetime in the cell. For example, inhibiting synthesis of either protein or phospholipid leads to a proportional decrease in the amount of both protein and phospholipid... 

Bednarek SV, Raikhel NV. Intracellular trafficking of secretory proteins. Plant... 

Kajava, A. V., and Steven, A. C. (2006). The Turn of the screw Variations of the abundant beta-solenoid motif in passenger domains of type V secretory proteins./. Struct. Biol. 155, 306-315. 

Nakahara, D., Lingappa, V., and Chuck, S. (1994). Translocational pausing is a common step in the biogenesis of unconventional integral membrane and secretory proteins. J. Biol. Chem. 269, 7617-7622. 

Insect OBPs are secretory proteins whose only posttranslational modification is the formation of three disulfide bridges [39,45] from six cysteine residues. That six cysteine residues are well conserved in OBPs from species of the same order is a hallmark of these proteins. The disulfide links of OBPs in a few species have been determined by analytical methods, first in the OBPs from B. mori [45,46]. As part of our attempt to get better insight into the structural biology of pheromone-binding proteins, we have determined the disulfide linkages... 

Zhang L, Whitsett JA, Stripp BR (1997) Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1. Biochim Biophys Acta 1350(3) 359-367... 

Rusinol, A.E., Cui, Z, Chen, M.H., and Vance, J.E., 1994, A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J. Biol. Chem., 269 27494-27502. 

Studies with VSV and SFV were the first to show that membrane glycoproteins make use of the same mechanisms used by secretory proteins to become segregated into the ER lumen (Katz et al., 1977 Rothman and Lodish, 1977 Wirth et al., 1977 Lingappa et al., 1978 ... 

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