Endoplasmic reticulumCamillo GolgiCisternaeVesiclesLysosomesMembranesProteins and lipidsEukaryotic cellsOrganelleProteinLipidsNucleusSecretory pathwayNeurodegenerative diseasesMoleculesEnzymesCytoplasmMicrotubulesCellularOriginateStacksSubcellularSacsFragmentationGlycoproteinsBodyKinasesIsolationComplexLocalizationComplexesPhysicianSaccharomycesFunctionThesisStructureSecretionTransCellsOrganizationGenes involvedProcesses
Endoplasmic reticulum27
- The common feature among Golgi is that they are adjacent to endoplasmic reticulum (ER) exit sites. (wikipedia.org)
- In most eukaryotes, the Golgi apparatus is made up of a series of compartments and is a collection of fused, flattened membrane-enclosed disks known as cisternae (singular: cisterna, also called "dictyosomes"), originating from vesicular clusters that bud off the endoplasmic reticulum. (wikipedia.org)
- The Golgi apparatus is a major collection and dispatch station of protein products received from the endoplasmic reticulum (ER). (wikipedia.org)
- Vesicles from the endoplasmic reticulum (via the vesicular-tubular cluster ) fuse with the cis-Golgi network and subsequently progress through the stack to the trans-Golgi network, where they are packaged and sent to the required destination. (wikidoc.org)
- This includes the productions of glycosaminoglycans or GAGs, long unbranched polysaccharides which the Golgi then attaches to a protein synthesized in the endoplasmic reticulum to form the proteoglycan . (wikidoc.org)
- Vesicles which leave the rough endoplasmic reticulum are transported to the cis face of the Golgi apparatus, where they fuse with the Golgi membrane and empty their contents into the lumen . (wikidoc.org)
- Usually, this apparatus is localized close to the nucleus , to be able to "receive" from the rough endoplasmic reticulum ( RER ), rich in ribosomes, the amino acid chains just synthesized, through vesicles. (microbiologiaitalia.it)
- Golgi apparatus is positioned near the nucleus It has 2 ends or faces, particularly cis face and transface The cis face is placed near the endoplasmic reticulum . (earthslab.com)
- Reticular vesicles from endoplasmic reticulum get in the Golgi apparatus through cisface The trans face is positioned near the cell membrane . (earthslab.com)
- The Golgi apparatus functions in association with the endoplasmic reticulum. (earthslab.com)
- Some proteins and glycoproteins synthesised in the rough endoplasmic reticulum (RER) are provided to the Golgi apparatus by transport vesicles The vesicles normally reach a cisterna called the cis face (" getting' side). (earthslab.com)
- Unlike the endoplasmic reticulum (ER) stress response, the Golgi stress response is relatively unexplored. (encyclopedia.pub)
- The Golgi Apparatus sorts, modifies, and packages proteins and other materials from the endoplasmic reticulum for storage in the cell or secretion outside the cell. (protopage.com)
- A Golgi apparatus is found in the cytoplasm of the cell next to the endoplasmic reticulum . (jotscroll.com)
- The Golgi apparatus is located and seen in between the cell membrane and the endoplasmic reticulum. (jotscroll.com)
- This is why the Golgi apparatus can be easily mistaken for the smooth endoplasmic reticulum . (jotscroll.com)
- The Golgi is called a perinuclear body and is near the endoplasmic reticulum. (jotscroll.com)
- As a result, when proteins come out of the endoplasmic reticulum, they go into the Golgi apparatus for further modification and processing. (jotscroll.com)
- The Golgi apparatus does many tasks in the cell although all tasks are associated with the movement of molecules from the endoplasmic reticulum to their various end destination. (jotscroll.com)
- As products move through the Golgi body from the endoplasmic reticulum, they are transferred continuously into new environments. (jotscroll.com)
- Golgi apparatus is involved in the packaging of various biomolecules such as proteins, lipids, etc. which are manufactured in the endoplasmic reticulum. (breldigital.com)
- PKG II secreted via the classical endoplasmic reticulum-Golgi apparatus secretory pathway blocks the activation of EGFR through phosporalting its threonine 406 and has an anti-tumor effect. (bvsalud.org)
- 2. How does the Golgi apparatus differ from the endoplasmic reticulum? (edurev.in)
- The Golgi apparatus and the endoplasmic reticulum (ER) are both involved in the processing and transport of proteins, but they have distinct functions. (edurev.in)
- May also mediate transport from the endoplasmic reticulum to the Golgi. (abcam.com)
- The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway sustaining the delivery of proteins from their site of synthesis in the endoplasmic reticulum to their final destination, the extracellular medium, the plasma membrane, and the endo-lysosomal system. (frontiersin.org)
- Endoplasmic reticulum and Golgi apparatus membranes,cytoplasmic vesicle. (novusbio.com)
Camillo Golgi8
- It was identified in 1897 by the Italian biologist and pathologist Camillo Golgi and was named after him in 1898. (wikipedia.org)
- It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system. (wikipedia.org)
- It was identified in 1898 by the Italian physician Camillo Golgi and was named after him. (wikidoc.org)
- It was the physician and histologist Camillo Golgi who first identified and described this organelle, already before the advent of the electron microscope, using specific histological stainings (Fig.1). (microbiologiaitalia.it)
- In 1898, Camillo Golgi described an "internal reticular apparatus" in cells stained using Golgi's method (silver stain). (histologyguide.org)
- Golgi apparatus or Golgi body or Golgi complex is a membrane-bound organelle, associated with the processing of proteins It exists in all the cells other than red blood cells It is called after the originator Camillo Golgi. (earthslab.com)
- Camillo Golgi was born on 7 July 1843 in the village of Corteno near Brescia, in the province of Brescia ( Lombardy ), at the time Kingdom of Lombardy-Venetia, today Italy. (wikipedia.org)
- The mammalian Golgi apparatus was first described by Camillo Golgi in 1998 as "apparato reticolare interno," "a fine and elegant network within the cell body … completely internal in the nerve cells" ( Golgi, 1898a , b ). (frontiersin.org)
Cisternae14
- This collection of cisternae is broken down into cis, medial, and trans compartments, making up two main networks: the cis Golgi network (CGN) and the trans Golgi network (TGN). (wikipedia.org)
- The compartmentalization of the Golgi apparatus is advantageous for separating enzymes, thereby maintaining consecutive and selective processing steps: enzymes catalyzing early modifications are gathered in the cis face cisternae, and enzymes catalyzing later modifications are found in trans face cisternae of the Golgi stacks. (wikipedia.org)
- Several rab proteins localise to the Golgi apparatus, the organelle consisting of stacked, flattened, membrane-bound cisternae through which newly-synthesised proteins are transited and modified, and where proteins and lipids are sorted and packaged for transport to other subcellular destinations. (bl.uk)
- The Golgi is composed of membrane-bound sacs known as cisternae . (wikidoc.org)
- The cisternae stack has five functional regions: the cis-Golgi network, cis-Golgi, medial-Golgi, trans-Golgi, and trans-Golgi network. (wikidoc.org)
- Through gemmation and endocytosis events, the vesicles carrying the protein material, deriving from the RER, merge with the cisternae in cis of the Golgi apparatus. (microbiologiaitalia.it)
- Numerous transport vesicles integrate to form cisternae on the cisface Inside the Golgi apparatus, enzymes customize the showing up proteins and glycoproteins. (earthslab.com)
- Little transport vesicles return local Golgi proteins to cisternae of the cis face for reuse. (earthslab.com)
- Golgi apparatus is a cellular organelle in eukaryotic organisms made up of a series of flattened stacked pouches called cisternae . (jotscroll.com)
- Cells expressing mutant huntingtin produced both an accumulation of clathrin adaptor complex 1 at the Golgi and an increase of clathrin-coated vesicles in the vicinity of Golgi cisternae as revealed by electron microscopy. (elsevierpure.com)
- Rough ER transport materials through the cell and produces proteins in sacks called cisternae (which are sent to the Golgi body, or inserted into the cell membrane). (enchantedlearning.com)
- This large reticulum comprises stacks of flattened membrane bound compartments called cisternae which are laterally linked to form the so-called Golgi ribbon. (frontiersin.org)
- They manifest as fragmentation-transformation of the Golgi ribbon into disconnected stacks, cisternae, tubules and vesicles, and as atrophy-loss of Golgi membrane material. (frontiersin.org)
- The Golgi apparatus (GA), also called Golgi body or Golgi complex and found universally in both plant and animal cells, is typically comprised of a series of five to eight cup-shaped, membrane-covered sacs called cisternae that look something like a stack of deflated balloons. (greatgreenwedding.com)
Vesicles14
- Proteins synthesized in the ER are packaged into vesicles, which then fuse with the Golgi apparatus. (wikipedia.org)
- These vesicles are transported by microtubule-based motor proteins and fuse together to form vesicular tubular clusters, subsequently arriving at the Golgi apparatus, a eukaryotic endomembrane organelle that often has a distinctive ribbon-like appearance. (jove.com)
- The apparatus of Golgi (Fig. 2) is constituted by a pile of flattened vesicles and delimited by a membrane. (microbiologiaitalia.it)
- Vesicles including glycoproteins and lipids are carried into Golgi apparatus Here, the glycoproteins and lipids are customized and processed. (earthslab.com)
- Golgi bodies have a major role in transporting, modifying, and packaging lipids and proteins into vesicles for delivery to specific areas in the cell. (jotscroll.com)
- Thus, when the glycoproteins are modified, they are transported by Golgi vesicles which bud off from one end of the Golgi bodies. (jotscroll.com)
- The primary importance of the Golgi apparatus in the cell is its ability to deliver vesicles or package various cell macromolecules products to various locations within the cell. (jotscroll.com)
- The vesicles are made from the Golgi network. (jotscroll.com)
- Actually, one of the functions of the Golgi apparatus is to generate new vesicles from the existing membrane of the Golgi apparatus. (jotscroll.com)
- It then put the glycoproteins and other substances that are made in the Golgi network into those vesicles. (jotscroll.com)
- Then the vesicles filled with the Golgi products move to the rest of the cell. (jotscroll.com)
- Secretory vesicles of the Golgi apparatus fuse and get incorporated into the cell membrane. (edumarz.com)
- Secretory vesicles and lysosomes originate from the Golgi apparatus. (edumarz.com)
- The golgi body packages proteins and carbohydrates into membrane-bound vesicles for "export" from the cell. (enchantedlearning.com)
Lysosomes9
- For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes . (wikidoc.org)
- Lysosomes are formed by the Golgi Apparatus. (protopage.com)
- Golgi Apparatus & Lysosomes - Cell Biology - Class 9 - Science for Class 9 2023 is part of CBSE Class 9 Biology(CELLS)-Videos & Documents by Let's tute preparation. (edurev.in)
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- Furthermore, inverse fluorescence recovery after photobleaching analysis for lysosomal-associated membrane protein-1 and mannose-6-phosphate receptor showed that the optineurin/Rab8-dependent post-Golgi trafficking to lysosomes was impaired in cells expressing mutant huntingtin or reducing huntingtin levels by small interfering RNA. (elsevierpure.com)
- Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). (abcam.com)
Membranes2
- siRNA-mediated depletion of these rabs and golgins revealed them to be important for the maintenance of Golgi structure and suggested that p115 is primarily recruited to Golgi membranes by its interaction with rab1 rather than its association with GM130. (bl.uk)
- Colocalization studies and Western blot analysis of isolated Golgi membranes showed a reduction of huntingtin in the Golgi apparatus of cells expressing mutant huntingtin. (elsevierpure.com)
Proteins and lipids4
- The primary function of the Golgi apparatus is to process and package the macromolecules such as proteins and lipids that are synthesised by the cell. (wikidoc.org)
- Hence, the Golgi complex process and packages proteins and lipids that are synthesized by the cell. (jotscroll.com)
- The Golgi apparatus is responsible for processing, packaging, and sorting proteins and lipids within the cell. (edurev.in)
- The ER is responsible for synthesizing proteins and lipids, while the Golgi apparatus modifies and packages these molecules. (edurev.in)
Eukaryotic cells3
- The Golgi apparatus (/ˈɡɒldʒi/), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. (wikipedia.org)
- The Golgi apparatus forms a part of the endomembrane system of eukaryotic cells. (wikidoc.org)
- The Golgi apparatus transports and modifies proteins in eukaryotic cells. (greatgreenwedding.com)
Organelle6
- In order to do so the Golgi transports substances such as nucleotide sugars into the organelle from the cytosol. (wikidoc.org)
- This organelle is also called a Golgi body or Golgi complex . (jotscroll.com)
- Well, even though they look similar, the Golgi apparatus happens to be an independent organelle with different functions. (jotscroll.com)
- The Golgi apparatus research field is so broad that an exhaustive review of this organelle is not doable here. (nih.gov)
- The issue starts with a summary on Golgi functional organization in neurons (Valenzuela and Perez) and the relation of this organelle with microtubules (Sanders and Kaverina) . (frontiersin.org)
- The Golgi apparatus is the central organelle mediating protein and lipid transport within the eukaryotic cell. (greatgreenwedding.com)
Protein14
- The cis-Golgi-localised rab protein, rabl, is shown to interact with the Golgi matrix/golgins GM130 and p115 while rab2 binds GM130 as well as a novel tethering factor named golgin-45. (bl.uk)
- A search for novel effectors of the trans-Golgi-localised rab protein, rab6, was also made, revealing specific interactions with the dynactin subunit p150glued and the dynactin/dynein accessory proteins BicD1 and BicD2. (bl.uk)
- Finally, the cis-Golgi rab-effector and matrix protein, GM130, is shown to have a hitherto unsuspected role in the activation of a family of Golgi-localised Ste20 kinases. (bl.uk)
- [4] Enzymes in the Golgi will polymerize several of these GAGs via a xylose link onto the core protein. (wikidoc.org)
- In addition a newly characterised anti-apoptotic protein, GAAP (Golgi anti-apoptotic protein), which almost exclusively resides in the Golgi, protects cells from apoptosis by an as-yet undefined mechanism (Gubser et al. (wikidoc.org)
- It goes without saying that Golgi's apparatus is much more complex and developed in cellular types engaged in intense protein activity. (microbiologiaitalia.it)
- Changes to proteins that occur at the level of the Golgi apparatus may be additions or even simplifications, depending on the fate of the protein. (microbiologiaitalia.it)
- The processed substances make their exit from Golgi apparatus through transface The Golgi apparatus exists in bigger numbers and is best established in cells that produce protein, such as the cells of the salivary glands or the pancreas. (earthslab.com)
- Golgi apparatus proteomics provides fundamental information for uncovering novel membrane proteins and posttranslational modification, protein secretory pathway, improved insights into Golgi apparatus function, interactions and cellular mechanisms, further exploring the pathogenesis of diseases associated with Golgi apparatus, and promoting development of targeted therapies. (creative-proteomics.com)
- Golgi apparatus proteins are analyzed by Multidimensional protein identification technology (MudPIT), which combines a cation exchange pre-fractionation and RP HPLC separation of tryptic peptides. (creative-proteomics.com)
- For example, Golgi apparatus protein function analysis, homology analysis and evolution analysis. (creative-proteomics.com)
- Efficient and stable protein extraction method: according to your sample types, we have optimized Golgi apparatus isolation protocol and protein extraction scheme, and increased the protein flux and extraction purity. (creative-proteomics.com)
- Also required for protein transport from the Golgi apparatus to the endosomes. (abcam.com)
- How have scientists studied dynamic protein movements through the Golgi? (greatgreenwedding.com)
Lipids1
- Major functions of Golgi apparatus are processing, packaging, labelling and shipment of proteins and other molecules like lipids to various parts of the cell. (earthslab.com)
Nucleus2
- In mammals, a single Golgi apparatus is usually located near the cell nucleus, close to the centrosome. (wikipedia.org)
- A single cell might consist of more than one Golgi apparatus, generally situated near the nucleus. (earthslab.com)
Secretory pathway1
- Golgi apparatus plays a critical role in post-translational modification and secretory pathway, and participates in various cellular activities, including apoptosis, mitosis, stress response, etc . (creative-proteomics.com)
Neurodegenerative diseases1
- Consistent with the MT dysfunction, we also observed other degenerative changes, such as neuritic degeneration, trafficking defects, and Golgi fragmentation, which are common pathological features shared by many human neurodegenerative diseases. (nih.gov)
Molecules4
- The Golgi also plays an important role in the synthesis of proteoglycans , molecules present in the extracellular matrix of animals , and it is a major site of carbohydrate synthesis. (wikidoc.org)
- Another task of the Golgi involves the sulfation of certain molecules passing through its lumen via sulphotranferases that gain their sulphur molecule from a donor called PAPs. (wikidoc.org)
- The Golgi is also capable of phosphorylating molecules. (wikidoc.org)
- From the apparatus of Golgi originate therefore two families of molecules: oligosaccharides with high content of mannose and oligosaccharides complexes. (microbiologiaitalia.it)
Enzymes1
- It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus. (wikipedia.org)
Cytoplasm2
- In experiments it is seen that as microtubules are depolymerized the Golgi apparatuses lose mutual connections and become individual stacks throughout the cytoplasm. (wikipedia.org)
- In yeast, multiple Golgi apparatuses are scattered throughout the cytoplasm (as observed in Saccharomyces cerevisiae). (wikipedia.org)
Microtubules3
- Localization and tubular connections of the Golgi apparatus are dependent on microtubules. (wikipedia.org)
- Organization of the plant Golgi depends on actin cables and not microtubules. (wikipedia.org)
- Furthermore, the recognition of Golgi-derived microtubules and their specific functions, the better understanding of Golgi transport processes, the recognition of the Golgi apparatus as a sensor of cellular stress and as trigger of Golgi-specific cell death pathways provide new hints to the molecular mechanisms underlying Golgi pathology. (frontiersin.org)
Cellular1
- The third part of this issue starts by posing the hypothesis of Farhan and colleagues that cellular stress can be the cause of Golgi fragmentation, which in turn amplifies cellular stress and leads to neurodegeneration (Alvarez-Miranda et al.) . (frontiersin.org)
Originate1
- Lamellar granules are intracellular granules that originate from the Golgi apparatus of keratinocytes in the stratum corneum. (medscape.com)
Stacks3
- In plants, Golgi stacks are not concentrated at the centrosomal region and do not form Golgi ribbons. (wikipedia.org)
- In plants, the individual stacks of the Golgi apparatus seem to operate independently. (wikipedia.org)
- Additionally, the ER is a continuous network of tubules and sac-like structures, while the Golgi apparatus is organized into flattened stacks of membrane-bound compartments. (edurev.in)
Subcellular3
- The subcellular localization of the Golgi apparatus varies among eukaryotes. (wikipedia.org)
- The subcellular localization of the Golgi apparatus varies among eukaryote s. (explained.today)
- For non specialists, Golgi is a very well known subcellular compartment involved in secretion and correct targeting of soluble and transmembrane proteins. (nih.gov)
Sacs1
- Golgi apparatus has multiple sacs that serve as chambers for different chemical reactions. (jotscroll.com)
Fragmentation1
- Neuritic degeneration and Golgi fragmentation were confirmed in primary cultures of dorsal root ganglia (DRG) neurons overexpressing alpha-syn. (nih.gov)
Glycoproteins3
- Golgi complex does not produce proteins but they modify the proteins by the addition of carbohydrates to the proteins, forming glycoproteins. (jotscroll.com)
- The Golgi apparatus is basically the site for the modification, completion, and exportation of secretory proteins and glycoproteins. (jotscroll.com)
- These glycoproteins then move out of the Golgi apparatus to the rest of the cell. (jotscroll.com)
Body2
- A Golgi body can be called the manufacturing and shipping center of the cell. (jotscroll.com)
- Thus, the Golgi body is also called the 'Traffic police' of the cell. (breldigital.com)
Kinases1
- [5] The Golgi itself contains resident kinases , such as casein kinases . (wikidoc.org)
Isolation1
- Construction of peptides and plasmids , RNA interference , Immunoelectron microscopy , Co-immunoprecipitation , N- glycosylation assay and Isolation of the Golgi apparatus were applied to investigate the secretory mechanism, and the targets and function of PKG II. (bvsalud.org)
Complex5
- The term "Golgi apparatus" was used in 1910 and first appeared in the scientific literature in 1913, while "Golgi complex" was introduced in 1956. (wikipedia.org)
- Several proteins at some point in their maturation pass through the Golgi complex. (jotscroll.com)
- However, as these proteins reach the Golgi complex, more modifications are made to them. (jotscroll.com)
- Together, our results indicate that mutant huntingtin perturbs post-Golgi trafficking to lysosomal compartments by delocalizing the optineurin/Rab8 complex, which, in turn, affects the lysosomal function. (elsevierpure.com)
- Figure 212 from Chapter 6 (Golgi Apparatus) of 'The Cell, 2nd Ed.' by Don W. Fawcett M.D. Secretory cells in Brunner's duodenal gland of the mouse have an extensive Golgi complex, with secretory granu. (cellimagelibrary.org)
Localization1
- Localization and tubular connections of the Golgi apparatus are dependent on microtubule s. (explained.today)
Complexes2
- for example, the antibody-secreting plasma B cells of the immune system have prominent Golgi complexes. (wikipedia.org)
- for example, the antibody-secreting plasma B cell s of the immune system have prominent Golgi complexes. (explained.today)
Physician1
- His father Alessandro Golgi was a physician and district medical officer, originally from Pavia. (wikipedia.org)
Saccharomyces1
- Pichia pastoris does have stacked Golgi, while Saccharomyces cerevisiae does not. (wikipedia.org)
Function3
- The implications of all these interactions for Golgi structure and function is discussed. (bl.uk)
- Which of the following is a function of the golgi apparatus? (breldigital.com)
- 1. What is the function of the Golgi apparatus in a cell? (edurev.in)
Thesis2
- This thesis focuses on Golgi-localised rab proteins and their effector proteins. (bl.uk)
- Inspired by Lombroso, Golgi wrote a thesis on the etiology of mental disorders , from which he obtained his M.D. in 1868. (wikipedia.org)
Structure5
- Owing to its large size and distinctive structure, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. (wikipedia.org)
- Some doubted the discovery at first, arguing that the appearance of the structure was merely an optical illusion created by the observation technique used by Golgi. (wikipedia.org)
- The structure of the Golgi is maintained by a matrix of proteins, many of which have now been shown to be rab-effector proteins. (bl.uk)
- Golgi apparatus forms a stacked structure. (edumarz.com)
- have been shown to affect Golgi structure or transport processes to and from the Golgi. (frontiersin.org)
Secretion1
- The Golgi apparatus is integral in modifying, sorting, and packaging these substances for cell secretion ( exocytosis ) or for use within the cell. (wikidoc.org)
Trans1
- Taken together, these experiments revealed that Vapyrin-bodies have an endosomal identity with trans-Golgi features, and that VAPYRIN interacts with a symbiotic R-SNARE of the VAMP721 family, that localizes to the same compartment. (frontiersin.org)
Cells4
- However, plant cells may contain hundreds of Golgi bodies. (jotscroll.com)
- Moreso, in plant cells, most of the cell wall material passes through the Golgi apparatus. (jotscroll.com)
- Golgi apparatus plays an important in plant cells as well. (edumarz.com)
- By confocal microscopy of A549 cells, we showed that the xylosides were taken up by the cells, but did not enter the Golgi apparatus where most of the glycosaminoglycan biosynthesis occurs. (lu.se)
Organization1
- Yet, neither the molecular mechanisms underlying the changes in the functional organization of the Golgi apparatus nor their precise relevance to neurodegeneration have yet been completely elucidated. (frontiersin.org)
Genes involved2
- Further analyses of C. neoformans mutant strains identified three mannosyltransferase genes involved in O-glycan extensions in the Golgi. (elsevierpure.com)
- It is suggested that oxidative stress, stress in the Golgi Apparatus, reduction in expression of the set of genes involved in the signaling pathway Epithelial Growth Factor Receptor (EGFR) and in the pathway of the metabolism of beta-amyloid peptide and alteration of the catalytic activity of D2 with consequent changes in serum levels of T3 and T4 may contribute to the development or as aggravating of these conditions. (bvsalud.org)
Processes1
- The Golgi apparatus is a real sorting center, which at the same time allows the maturation processes of proteins, thus dealing with post-translational modifications . (microbiologiaitalia.it)