Secretory Poly peptide

Neonatal Pulmonary Host Defense

Misty Good , ... Kerry McGarr Empey , in Fetal and Neonatal Physiology (Fifth Edition), 2017

Club Cell Secretory Protein (CC10, CC16)

Club cell secretory protein (CCSP) is one of the most arable proteins of the airway lining fluid. It is secreted past lodge cells, besides equally by serous and goblet cells of the proximal airways. 671 Structurally, CCSP is a small homodimeric poly peptide consisting of ii 8-kDa subunits aligned by disulfide links to form a hydrophobic pocket. 672 This pocket tin can bind phosphatidylcholine and phosphatidylinositol, and CCSP was originally postulated to participate in surfactant metabolism. CCSP has been noted to modulate inflammatory responses, suggesting a potential immunoregulatory role within the airways and alveoli. In vitro, CCSP has been shown to inhibit PMN chemotaxis, also every bit macrophage phagocytosis. 672 Its hydrophobic pocket allows CCSP to scavenge phospholipase A2 within the milieu, farther limiting PMN activation. 672 CCSP has likewise been shown to inhibit the production and bioactivity of IFN-γ. 672 Murine models of CCSP deficiency have attempted to further clarify the in vivo function of this protein. In a hyperoxic model of lung injury, CCSP-deficient animals exhibited higher lung levels of IL-1β, IL-vi, and IL-three, increased lung inflammation, and decreased survival rates. 673 In a model of adenoviral lung infection, CCSP deficiency resulted in an earlier, increased, inflammatory response; this was accompanied by increased expression of TNF, IL-1β, IL-half dozen, and chemokines (CCL3 and CCL2). 674 CCSP-scarce animals receiving an antigenic claiming showed increased levels of Th2 cytokines with exacerbated eosinophilic inflammation. 675 Finally, CCSP-deficient mice demonstrate increased expression of IgA. 676 The exaggerated cellular response seen in each of these models is consistent with the putative part of CCSP as an antiinflammatory molecule. LPS depresses CCSP gene expression in a dose-dependent style, suggesting that potent signals of infection may dampen CCSP secretion every bit required to permit an advisable inflammatory response. 677 In newborns, CCSP levels are detected in tracheal/alveolar aspirates obtained at birth and correlate with gestational age. Neonates with clinical signs of infection have increased CCSP levels, correlating inversely with tracheoalveolar fluid leukocyte counts. 678 Similarly, infants who after develop BPD demonstrate diminished inducibility of CCSP and mostly lower CCSP levels in their airway fluid, maybe contributing to the increased lung inflammation seen in this process. 679,680 In a study with newborn piglets who received surfactant and a recombinant homo club cell poly peptide, pulmonary compliance was improved. 681,682 In summary, CCSP appears to serve a homeostatic office in titrating inflammatory action within the air spaces of the lung. Although not classically viewed equally a cytokine, CCSP meets these criteria because it exhibits receptor-mediated signaling, regulates other cytokines and immune prison cell office, and is regulated in dose-dependent fashion by relevant biologic stimuli such as IFN and LPS.

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Book 2

Fred S. Gorelick , ... James D. Jamieson , in Physiology of the Gastrointestinal tract (Sixth Edition), 2018

39.4.4.i ER to Golgi

Secretory proteins are efficiently stored at high concentrations in zymogen granules by steps that sequentially enrich the proteins several hundred-fold over that plant in the ER lumen ( Fig. 39.13). 73,74 They are besides segregated away from other soluble proteins, most notably lysosomal enzymes, as they move to their terminal storage site. The first pace in the concentration process takes identify as nascent secretory proteins are preparing to be transported in vesicles from the ER. These vesicles sally from distinct protrusions from the RER, known every bit transitional elements, that are devoid of ribosomes and are shut to the Golgi complex (Fig. 39.9). After budding, the small (~   90   nm) vesicles with their nascent poly peptide cargo move to an intermediate compartment known every bit the vesicular-tubular complex (VTC). Proteins are then transferred from the VTC to the Golgi circuitous past directly fusion or by vesicles that bud from the VTC.

Fig. 39.13

Fig. 39.13. Acinar prison cell secretory proteins are concentrated in several compartments along the secretory pathway. The left panel demonstrates immunogold labeling used in immunogold techniques. Amylase is labeled with minor (5   nm gold) and chymotrypsinogen with larger (10 nm) gold particles.

 (Data with permission from Oprins A, Rabouille C, Posthuma Thousand, et al. The ER to Golgi interface is the major concentration site of secretory proteins in the exocrine pancreatic cell. Traffic 2001;2:831–8.)

Motion of nascent proteins from the ER is mediated past the add-on of the COPII coatamer protein complex to the cytoplasmic side of the ER membrane. The COPII coat proteins are required for cargo selection, vesicle budding from the ER, and forward trafficking. 75 The coat is sequentially assembled with the addition of the pocket-size GTPase, Sar1, followed past the soluble complexes of Sec23/24 and Sec13/31. Accessory proteins may function equally a scaffold for assembly and regulate the GTPase action of Sar1. The mechanisms for cargo selection are non fully understood (encounter Ref. 76). Some studies suggest that putative cargo may be full-bodied into a molecular scaffold at the transitional elements of the ER. 77 The selection of some transmembrane proteins for cargo appears to largely take identify through the binding of singled-out sequences on their cytoplasmic domain to Sec24 (reviewed in Ref. 78). The COPII proteins are concentrated on the forming vesicles and transmembrane proteins that demark Sec24 are also enriched. Transmembrane proteins are enriched v- to 10-fold in the COPII vesicle every bit compared to the nearby ER.

The mechanism for concentrating soluble proteins remains uncertain, but several findings demonstrate that information technology must be unlike than transmembrane proteins. First, while transmembrane proteins are greatly concentrated as they sally in COPII vesicles, soluble proteins do non become substantially full-bodied over the ER lumen until they reach the VTC. 74 For the acinar jail cell, dramatic differences amongst concentrating secretory proteins emerging from the ER have been observed (Fig. 39.13). Second, mechanisms described for concentrating soluble glycoproteins in other systems are simply relevant to a limited number of pancreatic proteins. Thus, the saccharide moiety on some soluble glycosylated proteins binds to the lectin domain on the luminal domain of the transmembrane protein, ERGIC-58. Information technology is possible that glycosylated pancreatic secretory poly peptide such as GP2 and muclin are concentrated as they leave the ER past binding to ERGIC-58. However, other mechanisms must account for the concentration of most secretory proteins observed in the acinar jail cell. As shown in Fig. 39.13, concentration of acinar cell secretory proteins is non uniform, with differences of over an guild of magnitude being observed for amylase, chymotrypsin, and procarboxypeptidase A, and occurs at multiple compartments in the secretory pathway. 74 Information technology is possible that zymogen granule membrane proteins may participate in the concentration of exportable proteins. The net result of the enrichment mechanism is to concentrate soluble proteins such as amylase, trypsinogen, and chymotrypsinogen ten- to 20-fold between the ER lumen and the Golgi complex and fifty-fifty further enrichment equally they movement toward the zymogen granule.

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Filamentous Fungal Cultures – Process Characteristics, Products, and Applications

Hesham A. El-Enshasy , in Bioprocessing for Value-Added Products from Renewable Resources, 2007

6.1 Furnishings of micromorphology

Secretory proteins begin their journey to the extracellular medium by inbound the endoplasmic reticulum (ER). In the ER, proteins are folded and tin undergo distinct modifications such every bit glycosylation, disulfide bridge germination, phosphorylation, and subunit associates. Subsequently, proteins get out the ER packed in transport vesicles and head to the Golgi compartment, where additional modifications can take place such every bit further glycosylation and peptide processing. Finally, again packed in secretory vesicles, proteins are directed to the plasma membrane, from where they are secreted. In some cases, the proteins do not reach the extracellular space, but are targeted to an intracellular compartment, such as the vacuole, either to get resident proteins or to undergo proteolytic degradation [ 175]. Most recent studies bespeak that poly peptide secretion occurs at the apical or subapical regions [176]. Recent work has reinforced this hypothesis [177–179]. Using the novel glucoamylasegreen fluorescence fusion protein (GLA-GFP) equally a secretion reporter to study protein secretion in A. niger, Gordon et al. [178] observed that GFP fluorescence was predominant at the hyphal apices and showed that this approach is a promising tool for further research in this field, as information technology allows in vivo monitoring of protein secretion. The apical localization of poly peptide secretion has led to the suggestion of employing morphological mutants displaying an increased apical surface, i.due east., hyperbranching mutants, as supersecreting strains [179]. Growth morphology can also affect the last product yield of a heterologous protein by indirectly affecting the secretion of extracellular proteases. Xu et al. [180] showed a direct relationship between protease secretion and growth morphology in recombinant A. niger. The transformation of growth from filamentous to pellet form increased the heterologous poly peptide production equally a issue of a significant reduction in native fungal proteases. Thus, this bioprocessing strategy tin exist effectively used to inhibit protease activeness in filamentous fungi and thereby enhance heterologous protein production.

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Peptide Hormones, Intracellular Transport

Gerard J.M. Martens , in Encyclopedia of Endocrine Diseases, 2004

Send From Er To Golgi And Through The Golgi Complex

Once secretory proteins are properly folded and modified in the ER, they move to specialized regions, the ER export sites, and are packaged in coated, irregularly shaped send vesicles. Post-obit uncoating, the transport vesicles form vesicular–tubular clusters [VTCs; also chosen the ER–Golgi intermediate compartment (ERGIC)] that move forth microtubules to the Golgi. ER-resident proteins (such equally the folding enzymes) contain retention and retrieval signals to hold them in this compartment. For instance, lumenal ER proteins contain the tetrapeptide retrieval sequence Lys-Asp-Glu-Leu, in unmarried-letter code KDEL, at their carboxyl terminus and these proteins are retrieved by the KDEL receptor. Although it is not clear whether a bespeak is needed for secretory proteins to exit the ER, receptors accept been proposed to be involved in their exit from the ER. One example concerns ERGIC-53, a recycling type I transmembrane poly peptide with an ER retention motif that functions as a mannose-bounden lectin to extract secretory glycoproteins from the ER. Furthermore, soluble secretory proteins may exist transported via the p24 family unit of type I transmembrane putative cargo receptors that are major constituents of the ship vesicles and continuously recycle between the ER and Golgi with their short, carboxy-terminal cytoplasmic domains acting equally ER export or retrieval signals by binding cytoplasmic coat protein complexes (COP-I and -Ii). Each of the send steps connecting the ER and the Golgi, and connecting the Golgi compartments to one another, is unidirectional and energy- and GTP-dependent. Small GTP-binding proteins (20–30 kDa, e.g., the Rab proteins) are distributed throughout the secretory pathway with distinctive subcellular locations and regulate vesicular trafficking betwixt the subcompartments. In improver, the traffic is regulated by integral membrane proteins [vesicular soluble N-ethylmaleimide-sensitive attachment protein receptors (five-SNAREs) and target (t)-SNAREs] for docking the vesicle to the membrane of the acceptor compartment and soluble proteins (NSF and SNAPs) to initiate vesicle fusion. In this vesicular model of protein ship, all anterograde (forward) and retrograde (backward) intra-Golgi steps involve transport simply via vesicles. Alternatively, a nonvesicular transport machinery may be present in which Golgi cisternae grade at the cis-face of the stack, probably by VTC fusion, and so progressively mature into trans-cisternae (cisternal maturation model). In this model, cisternae (or intermittent tubular continuities) deport secretory cargo through the stack in the anterograde direction, and vesicles send Golgi enzymes in the retrograde direction, allowing cisternal maturation to occur by progressive uptake of material from older stacks. At the TGN, the cisternae ultimately atomize and evolve into a collection of secretory vesicles, including immature secretory granules.

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Lung Resident Stem Cells

Mariana Alves Antunes , ... Patricia Rieken Macêdo Rocco , in Resident Stalk Cells and Regenerative Therapy, 2013

Clara and Variant-Clara Cells

Clara cell secretory protein (also known as CCSP, CC10, CC16, Clara cell antigen, secretoglobin, and uteroglobin) is the most abundant secretory protein found in airway surface fluid. There is evidence for a role of CCSP in homeostasis and repair, and as a potential biomarker of lung injury or disease. Clara cells, the almost agile producers of CCSP in lung, are found in bronchiolar epithelium and respiratory bronchioles ( Fig. six.1). Several subpopulations of CCSP-expressing cells have been suggested as truthful airway stem cells, including Clara cells [27,32,33] and variant-Clara cells, likewise known as octamer-binding transcription gene 4 (Oct-4)-expressing stalk cells [34], pulmonary neuroendocrine cells [7,eight,35,36], and bronchoalveolar stem cells [10].

Classical Clara cells nowadays functional properties of differentiated cell types in their quiescent state, but they may change to an active proliferative state with properties like to a transient-amplifying prison cell after injury. Clara cells express high levels of cytochrome P450 monooxygenases (specialized in metabolism of toxins), making them susceptible to toxicant-induced injury and expiry. Naphthalene, an environmental toxin institute in cigarette smoke and mothballs, only becomes toxic afterward its metabolism past cytochrome P450, making it a common experimental system for studying Clara cell injury.

Neuroendocrine cells take besides been speculated equally resident stalk cells. Yet, bear witness suggests that these cells may not be real airway stem cells but rather that they participate in the microenvironment necessary for stem jail cell expansion [12]. These cells are primordially organized into a discrete innervated zone within neuroepithelial bodies (NEBs) in the airway (Fig. 6.2). Through the action of a number of neuropeptides, NEBs seem to be involved in regulating embryonic lung growth and maturation [37]. Ii populations of label-retaining cells accept been identified within the NEBs: one expressing the pulmonary neuroendocrine cell (PNEC)-specific marker calcitonin gene-related peptide (CGRP) and one subpopulation of Clara cell secretory protein (CCSP)-expressing cells. These cells have been associated with epithelial regeneration later on naphthalene-induced classical Clara-cell ablation. Evidence demonstrates that afterwards selective ablation of CCSP-expressing cells, there is an increment in proliferative rate and hyperplasia of PNECs; however, it is not sufficient to effectively regenerate a normal epithelium [36]. This indicates that PNECs are not themselves capable of renewing CCSP-expressing cell-depleted airway epithelium, and that naphthalene-resistant CCSP-expressing cells of the NEBs have a disquisitional function in airway renewal after transient-amplifying jail cell ablation. Nonetheless, previous findings suggest that, during repair, CCSP-expressing cells that are shut to NEBs in developed lung take a higher proliferative charge per unit [36], and also that during development airway epithelial cell proliferation decreases every bit a function of increasing distance from the NEBs [38,39]. These information suggest that PNEC-derived paracrine factors might play a role in regulating epithelial prison cell differentiation and proliferation during fetal lung development and possibly in the normal or injured developed lung.

The term bronchoalveolar stem cell (BASC) reflects the ability of cultured CCSP/SP-C (SP-C, surfactant protein C) dual positive cells to express markers of Clara cells (CCSP positive (cells) and alveolar epithelial type 2 cells (SP-C positive cells), and to originate alveolar type 1 cells (Aquaporin 5 positive cells). These are rare cells (one to 2 cells per bronchoalveolar duct junction) with cuboidal morphology. BASC do not express the cytochrome P450 enzyme CYP2F2, which converts naphthalene into its toxic dihydrodiol metabolites, and for this reason, survive injury. BASC tin be identified by their expression of cell-surface protein CD34 and Sca-1 (both markers are unremarkably expressed in hematopoietic stem cells) and deprived expression of mature hematopoietic prison cell CD45 and platelet-endothelial prison cell adhesion molecule (PECAM, for hematopoietic and endothelial lineages exclusion) past FACS. Immunophenotyping of FACS-sorted populations using the CCSP and SP-C markers has determined that Sca-1+, CD45−, and PECAM− populations contain BASC. Post-obit distal airway injury using naphthalene and alveolar injury using bleomycin, resistant bronchoalveolar stem cells are stimulated to proliferate and originate daughter cells capable of renewing the airway and alveolar epithelium [11,20].

Several other stem prison cell markers have been identified in cultured lung, including Oct-iv+, a robust marker of pluripotency for both mouse and man embryonic stem cells [34]. Using serum-free choice media, neonatal and adult lung-derived Oct-four+ epithelial colony cells may be obtained. In add-on to Oct-4, neonatal lung cells also express other stem jail cell markers such as stage-specific embryonic antigen 1 (SSEA-1), Sca-one, and CCSP, only not c-Kit, CD34, and p63, suggesting an alternative subpopulation of Clara cells that take been implicated as lung stalk/progenitor cells. In summary, the detection of Oct-4+ long-term BrdU label-retaining cells at the bronchoalveolar duct junction of neonatal lungs and the in vitro differentiation of cultured cells into alveolar epithelial type-2- and type-1-similar cells suggest these October-4+ cells as putative neonatal lung stem/progenitor cells.

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The Pancreatic Beta Cell

Ming Liu , ... Peter Arvan , in Vitamins & Hormones, 2014

ii.1 Secretory protein translocation into the ER

For secretory proteins including preproinsulin, information technology is the bespeak peptide that drives the targeting of nascent polypeptides from the cytosol to the ER, the entry point into the secretory pathway ( Blobel & Dobberstein, 1975; Rapoport, 2007). Signal peptides are typically located at the N-terminus of secretory proteins and are on average twenty–30 residues in length. Signal peptides more often than not contain iii regions: an due north-region with hydrophilic and positive charge residues; a central core h-region with 5–xv hydrophobic residues; and a more polar c-region containing a signal peptidase cleavage site (von Heijne, 1998; Zheng & Gierasch, 1996). Early studies showed that, except for the h-region, signal sequences were simple, interchangeable, tolerant of a wide range of mutations, and even able to direct the ER targeting of proteins expressed in evolutionarily distant organisms (Gierasch, 1989; Talmadge, Stahl, & Gilbert, 1980). These early on studies implied that, besides directing the nascent polypeptide to the secretory pathway, signal sequences might not play an important function in regulating poly peptide biosynthesis. However, more than contempo prove indicates that variation of bespeak sequences tin can indeed bear upon protein targeting and translocation, signal peptide cleavage, also equally postcleavage events (Hegde & Bernstein, 2006; Rane, Chakrabarti, Feigenbaum, & Hegde, 2010; Swanton & High, 2006; Zhang, Rashid, Wang, & Shan, 2010). Indeed, variation of signal sequences may underlie a more complex role in regulating protein synthesis and targeting under sure pathophysiological conditions, for instance, ER stress (Hegde & Bernstein, 2006; Swanton & High, 2006).

Protein translocation into the ER can occur either cotranslationally, during which translocation is concomitant with protein synthesis, or posttranslationally, in which translocation occurs subsequently a polypeptide has been fully translated in the cytosol (Mitra, Frank, & Driessen, 2006). In mammalian cells, it appears that the efficiency of translocation of preproteins less than 100 amino acids in length relies strongly on Sec62-dependent posttranslational translocation mechanisms. Conversely, preproteins larger than 160 residues undergo exclusively signal recognition particle (SRP)-dependent cotranslational translocation, whereas preproteins of intermediate (120–160 residues) length can employ both the SRP pathway and Sec62 (Lakkaraju et al., 2012). At to the lowest degree 3 steps are involved in protein translocation from the cytosol to the ER: (ane) recognition and targeting of nascent polypeptides to the ER membrane; (two) translocation of proteins beyond the ER membrane; and (3) betoken peptide cleavage, poly peptide folding, and maturation in the ER. Hither, rather than more than extensive reviews of poly peptide targeting and translocation beyond the ER membrane (Cross, Sinning, Luirink, & High, 2009; Driessen & Nouwen, 2008; Rapoport, 2007), we focus on fundamental events likely to be of import for preproinsulin, highlighting contempo advances in understanding how defects in these events may crusade pancreatic beta cell failure and diabetes.

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Prohormone Convertase 1/3

Mirella Vivoli , Iris Lindberg , in Handbook of Biologically Active Peptides (Second Edition), 2013

Discovery and General Features of PC1/three

Many secretory proteins and peptide precursors are subjected to intracellular express proteolysis, a procedure essential for acquisition of bioactivity. The enzymes responsible for this intracellular cleavage have been characterized in molecular and functional terms and vest to an evolutionarily conserved family of serine proteases related to the bacterial enzyme subtilisin and the yeast processing protease kex2 or kexin (reviewed in Ref. 28). In humans, PC1/three is encoded by the PCSK1 gene located on chromosome 5 and consists of 14 exons. Because of the homology of their catalytic domains to that of the bacterial enzyme subtilisin, these enzymes take been termed subtilisin-like proprotein convertases (SPCs or PCs). 28 Thus far, vii mammalian PCs take been identified, and their nomenclature has been standardized every bit follows: PC1/iii (previously known as PC1, PC3 and sPC3); PC2; furin; PACE4; PC4; PC5/6; and PC7/viii (previously known besides equally sPC7, LPC, and PC8). All these enzymes specialize in the cleavage of basic residues within the general motif Arg-(10)north-Arg↓ where n   =   0, ii, 4, 6 and X is any amino acrid except Cys or Pro. Two other enzymes, subtilisin/kexin-like isozyme-1 (also known as SKI-1 and site-one protease) and PCSK9, which perform cleavages at hydrophobic residues (reviewed in Ref. 30), are also present inside the secretory pathway. The conservation of catalytic domains among these enzymes suggests a common evolutionary origin for PC genes; over time, ancestors of these enzymes have probably undergone duplications, insertions, translocations, and/or deletions to generate the current family unit.

PC1/3 was cloned in 1991 every bit the third PC to be identified; equally early every bit 1988, Hutton and colleagues described a proinsulin-processing enzyme in insulinoma granules, which they termed "Type I proinsulin converting endopeptidase," which was after identified as PC1/three. 28 Analysis of the tissue expression and cellular localization of the cloned enzyme confirmed that this enzyme is establish in dense core secretory granules within neuroendocrine tissues where it plays a pivotal role in the processing of neuropeptide and endocrine precursors. In this chapter, we review essential data concerning PC1/iii, focusing on the work of the final decade.

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Salivary Gland Secretion

Marcelo A. Catalán , ... James East. Melvin , in Physiology of the Gastrointestinal Tract (Fifth Edition), 2012

45.9 Factors Modulating Sorting of Secretory Proteins

The sorting of secretory proteins into granules is based on intrinsic structural information or specific components in the vesicles. 166 Both active and passive sorting models have been postulated to sort proteins into the regulated secretion pathway. 137 The active mechanism, 137 based on receptor-mediated trafficking, 167 requires binding of a secretory protein to its receptor on the intraluminal surface of the granule to facilitate storage of the protein 168 ; for case, proline-rich proteins in parotid acinar cells 169–171 and chromogranin B in neuroendocrine cells. 172 In contrast, the passive mechanism 137 requires condensation or aggregation of the regulated secretory protein. 173–175 Although there is no restriction for entry of secretory proteins into the granule, proteins that aggregate and course complexes tend to exclude proteins that neglect to aggregate, especially in the trans-Golgi. 137,168,176

Numerous factors regulate the targeting, storage, and release of secretory proteins such as pH, ion composition, and mail service-translational modifications. Intragranular pH has been suggested to play a crucial role in storage and retaining proteins within granules. For example, an alkaline pH promotes storage of bones proline-rich proteins, 177 whereas parotid secretory protein and acidic epididymal glycoprotein are poorly retained within granules with an elevated pH. 178 Polarized secretion of man growth hormone expressed in the secretory granules of rat submandibular glands 179 is significantly increased when acidified. 180 Monovalent ions "leak" from the granule equally it matures, 181,182 whereas divalent cations are retained during granule maturation. 183 Calcium and other multivalent cations likely serve as electrostatic bridges between negatively charged molecules, 184 facilitating the aggregation of mucins in exocrine cells and chromogranins in endocrine cells. 185,186 Post-translational modifications, such as sulfation, tin also human activity every bit important signals for sorting and storage of secretory proteins in rat parotid gland 187 and endocrine glands. 137 Sulfated proteoglycans such as chondroitin sulfate promote storage of acidic proline-rich proteins present in rat parotid acinar cells. 137

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Molecular Cell Biological science

Z. Chang , in Encyclopedia of Cell Biology, 2016

Abstract

Biogenesis of secretory proteins in eukaryotic cells largely occurs in the endoplasmic reticulum (ER). The precursor nascent polypeptide chain is recognized and translocated into the ER lumen co- or mail service-translationally through the Sec translocon of the ER membrane. The poly peptide then matures (folded, assembled and modified), as facilitated and monitored by many folding factors. Only correctly folded/assembled proteins are further transported. Unfolded proteins might be retained and degraded via the ER-associated deposition (ERAD) pathway and their accumulation triggers the unfolded poly peptide response (UPR) that helps to restore ER homeostasis. Malfunctioning of the ER protein biogenesis is linked to many hereditary folding diseases.

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Breakthrough Leaps in Biochemistry

Anil Day , Joanna Poulton , in Foundations of Modern Biochemistry, 1996

Poly peptide Targeting and Complex Assembly

Different animal secretory proteins which are transported during their synthesis on membrane-bound ribosomes (see Chapter five), the small subunit of Rubisco is completely synthesized in the cytoplasm and then transported into chloroplasts. This observation provided i of the first exceptions to the view, prevalent at the time, that cotranslation was necessary for protein transport across membranes (Ellis, 1979). The import of the small subunit of Rubisco into isolated chloroplasts requires an N-terminal transit peptide which is removed subsequently entry into the chloroplast. Many nuclear-encoded mitochondrial proteins are as well synthesized as precursors with an Due north-final presequence that is necessary for import into mitochondria (Neupert and Schatz, 1981).

Studies on the assembly of Rubisco holoenzyme, which is composed of eight large subunits and eight small subunits, showed the requirement for a large subunit binding protein. The binding protein is oligomeric and consists of 2 types of subunit α6βsix. It acts to foreclose assemblage of large subunits and ensures their right folding and assembly into Rubisco holoenzyme. It acts every bit a "molecular chaperone" (Ellis, 1987), a role showtime ascribed to nucleoplasmin (Laskey et al., 1978). This pop term has since grown to encompass an expanding list of proteins (Ellis and van der Vies, 1991). Chaperonins are homologous chaperone proteins present in bacteria, mitochondria, and plastids. The large subunit binding protein for Rubisco was the get-go chaperonin to be described.

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