Secretory pathway of cellulase: a mini-review.
Ontology highlight
ABSTRACT:
SUBMITTER: Yan S
PROVIDER: S-EPMC4177124 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Publications
Secretory pathway of cellulase: a mini-review.
Biotechnology for biofuels 20131202 1
Cellulase plays an important role in modern industry and holds great potential in biofuel production. Many different types of organisms produce cellulase, which go through secretory pathways to reach the extracellular space, where enzymatic reactions take place. Secretory pathways in various cells have been the focus of many research fields; however, there are few studies on secretory pathways of cellulases in the literature. It is therefore necessary and important to review the current knowledg ...[more]
Similar Datasets
Project description:Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until only recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.
| S-EPMC4577305 | biostudies-literature
Project description:The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs.
| S-EPMC120783 | biostudies-literature
Project description:GM1 gangliosidosis is a progressive, neurosomatic, lysosomal storage disorder caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase. Absent or reduced β-galactosidase activity leads to the accumulation of β-linked galactose-containing glycoconjugates including the glycosphingolipid (GSL) GM1-ganglioside in neuronal tissue. GM1-gangliosidosis is classified into three forms [Type I (infantile), Type II (late-infantile and juvenile), and Type III (adult)], based on the age of onset of clinical symptoms, although the disorder is really a continuum that correlates only partially with the levels of residual enzyme activity. Severe neurocognitive decline is a feature of Type I and II disease and is associated with premature mortality. Most of the disease-causing β-galactosidase mutations reported in the literature are clustered in exons 2, 6, 15, and 16 of the GLB1 gene. So far 261 pathogenic variants have been described, missense/nonsense mutations being the most prevalent. There are five mouse models of GM1-gangliosidosis reported in the literature generated using different targeting strategies of the Glb1 murine locus. Individual models differ in terms of age of onset of the clinical, biochemical, and pathological signs and symptoms, and overall lifespan. However, they do share the major abnormalities and neurological symptoms that are characteristic of the most severe forms of GM1-gangliosidosis. These mouse models have been used to study pathogenic mechanisms, to identify biomarkers, and to evaluate therapeutic strategies. Three GLB1 gene therapy trials are currently recruiting Type I and Type II patients (NCT04273269, NCT03952637, and NCT04713475) and Type II and Type III patients are being recruited for a trial utilizing the glucosylceramide synthase inhibitor, venglustat (NCT04221451).
| S-EPMC8446533 | biostudies-literature
Project description:Primary open angle glaucoma (POAG) is a leading cause of late onset, progressive, irreversible blindness and, although its etiology is poorly understood, elevated intraocular pressure (IOP) often appears to be a contributory factor. Proteomic and Western analyses of trabecular meshwork (TM) from patients with POAG and age-matched controls originally implicated cochlin as possibly contributing to glaucoma pathogenesis. Cochlin deposits were subsequently detected in glaucomatous but not in control TM and older glaucomatous TM was found to contain higher levels of cochlin and significantly lower amounts of collagen type II. More recently, similar results were reported in DBA/2J mice, which at older ages develop elevated IOP, retinal ganglion cell degeneration, and optic nerve damage. Notably, cochlin was absent in TM from C57BL/6J, CD1, and BALBc/ByJ mice, which do not exhibit elevated IOP or glaucoma. Cochlin was found in the TM of very young DBA/2J mice, prior to elevated IOP, suggesting that over time the protein may contribute to the events leading to increased IOP and optic nerve damage. Here we review these findings and describe how future studies in DBA/2J mice can help resolve whether cochlin plays a causal role in mechanisms of POAG and elevated IOP.
| S-EPMC1483214 | biostudies-literature
Project description:Forensic pathologists are routinely confronted with unclear causes of death or findings. In some scenarios, it can be difficult to answer the specific questions posed by criminal investigators or prosecutors. Such scenarios may include questions about wound vitality or causes of death when typical or landmark findings are difficult to find. In addition to the usual subsequent examinations to clarify unclear causes of death or special questions, immunohistochemical analysis has become increasingly important since its establishment in the early 40s of the 20th century. Since then, numerous studies have been conducted to determine the usefulness and significance of immunohistochemical investigations on various structures and proteins. These proteins include, for example, aquaporins, which belong to the family of water channels. They enable the transport of water and of small molecules, such as glycerol, through biological channels and so far, 13 classes of aquaporins could have been identified in vertebrates. The classic aquaporin channels 1, 2, 4 and 5 are only permeable to water. The aquaporin channels 3, 7, 9, and 10 are also called aquaglycerolporins since they can also transport glycerol. This mini review discusses the immunohistochemical research on aquaporins, their range of applications, and respective forensic importance, their current limitations, and possible further implementations in the future.
| S-EPMC8718671 | biostudies-literature
Project description:ObjectiveOur focus was on the determination of the growing number of youths of every race and ethnicity, diagnosed with obesity and its co-morbidities in the Caribbean. We reviewed the causes and strategies to combat obesity, and the implications of the fast food industry in enabling the escalation of obesity.MethodsWe consulted several databases such as PubMed, MEDLINE, the Obesity Gene Map Database, and the USEPA Toxicity Reference Database. Organizations such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Organization for Economic Co-operation and Development (OECD) and the Pan American Health Organization (PAHO) were used as information sources.ResultsTransgenerational effects and triggers like obesogens, pathogens, environmental stress, antibiotics and gut microbiota are some of the causes of obesity, and some of these triggers are imprinted epigenetically early in embryonic development, leading to lifelong obesity. With an estimated population of 42 million in the Caribbean, the economic cost of obesity, including medical, absenteeism, presenteeism, insurance, disability, direct and indirect cost, was estimated cost of 68.5 billion USD with 88.2 million quality-adjusted life years lost.ConclusionGenome-wide association studies have established that genetics play a role in the aetiology of this "non-communicable" disease. While the development of personalized interventions according to genotype is futuristic, we must focus on effective nutrition and physical education classes in schools and establishing monitoring programmes using simple tools such as scales and tape measures as suggested intervention. A Pigovian tax to control the fast food industry is mandatory. Nevertheless, lifestyle adjustment, including alterations in diet and increased physical activity, continues to be a sound recommendation.
| S-EPMC4763901 | biostudies-literature
Project description:Osteoporosis is a major cause of fractures and associated morbidity in the aged population. The pathogenesis of osteoporosis is multifactorial; whereas traditional pathophysiological concepts emphasize endocrine mechanisms, it has been recognized that also components of the immune system have a significant impact on bone. Since 2000, when the term 'osteoimmunology' was coined, novel insights into the role of inflammatory cytokines by influencing the fine-tuned balance between bone resorption and bone formation have helped to explain the occurrence of osteoporosis in conjunction with chronic inflammatory reactions. Moreover, the phenomenon of a low-grade, chronic, systemic inflammatory state associated with aging has been defined as 'inflamm-aging' by Claudio Franceschi and has been linked to age-related diseases such as osteoporosis. Given the tight anatomical and physiological coexistence of B cells and the bone-forming units in the bone marrow, a role of B cells in osteoimmunological interactions has long been suspected. Recent findings of B cells as active regulators of the RANK/RANKL/OPG axis, of altered RANKL/OPG production by B cells in HIV-associated bone loss or of a modulated expression of genes linked to B-cell biology in response to estrogen deficiency support this assumption. Furthermore, oxidative stress and the generation of advanced glycation end products have emerged as links between inflammation and bone destruction.
| S-EPMC4821368 | biostudies-other
Project description:We present the folding pathway model of mini-protein BBA5, a bundle of secondary structures, ?-helix and ?-hairpin, by using action-derived molecular dynamics (ADMD) simulations. From ten independent ADMD simulations, we extracted common features of the folding pathway of BBA5, from which we found that the early stage chain compaction was followed by the formation of C-terminal ?-helix. The N-terminal ?-hairpin was observed to form only after ?-helix was stabilized. This result is in good agreement with the experimental observation that BBA5 mutants were moderately cooperative folders, and their C-terminal helical fragments were of higher secondary structure propensity while the N-terminal hairpin fragments were of a random coil spectrum. We found that the most flexible part of BBA5 is the N-terminal four residues. Although both are made of the identical ??? motif, the secondary structure formation sequence of BBA5 is found to be different from that of FSD-1. Finally, a description of the folding pathway in terms of principal component analysis is presented to characterize the folding dynamics in reduced dimensions. With only three principal components, we were able to describe 83.4% of the pathway.
| S-EPMC4592707 | biostudies-literature
Project description:Newly synthesized secretory granule content proteins are delivered via the Golgi complex for storage within mature granules, whereas constitutive secretory proteins are not stored. Most soluble proteins traveling anterograde through the trans-Golgi network are not excluded from entering immature secretory granules, whether or not they have granule-targeting signals. However, the ;sorting-for-entry' hypothesis suggests that soluble lumenal proteins lacking signals enter transport intermediates for the constitutive secretory pathway. We aimed to investigate how these constitutive secretory proteins are sorted. In a pancreatic beta-cell line, we stably expressed two lumenal proteins whose normal sorting information has been deleted: alkaline phosphatase, truncated to eliminate its glycosylphosphatidylinositol membrane anchor (SEAP); and Cab45361, a Golgi lumenal resident, truncated to eliminate its intracellular retention (Cab308Myc). Both truncated proteins are efficiently secreted, but whereas SEAP enters secretory granules, Cab308Myc behaves as a true constitutive marker excluded from granules. Interestingly, upon permeabilization of organelle membranes with saponin, SEAP is extracted as a soluble protein whereas Cab308Myc remains associated with the membrane. These are among the first data to support a model in which association with the lumenal aspect of Golgi and/or post-Golgi membranes can serve as a means for selective sorting of constitutive secretory proteins.
| S-EPMC2547412 | biostudies-literature
Project description:Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein folding facilitators, misfolding can occur quite frequently. To maintain protein homeostasis, eukaryotes have evolved a series of protein quality-control checkpoints. When secretory pathway quality-control pathways fail, stress response pathways, such as the unfolded protein response (UPR), are induced. In addition, the ER, which is the initial hub of protein biogenesis in the secretory pathway, triages misfolded proteins by delivering substrates to the proteasome or to the lysosome/vacuole through ER-associated degradation (ERAD) or ER-phagy. Some misfolded proteins escape the ER and are instead selected for Golgi quality control. These substrates are targeted for degradation after retrieval to the ER or delivery to the lysosome/vacuole. Here, we discuss how these guardian pathways function, how their activities intersect upon induction of the UPR, and how decisions are made to dispose of misfolded proteins in the secretory pathway.
| S-EPMC6781448 | biostudies-literature