Cisterna

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A cisterna (pl.: cisternae) is a flattened membrane vesicle found in the endoplasmic reticulum and Golgi apparatus. [1] Cisternae are an integral part of the packaging and modification processes of proteins occurring in the Golgi. [2]

Contents

Function

Proteins begin on the cis side of the Golgi (the side facing the ER) and exit on the trans side (the side facing the plasma membrane). [2] Throughout their journey in the cisterna, the proteins are packaged and are modified for transport throughout the cell. [2] The number of cisterna in the Golgi stack is dependent on the organism and cell type. [3] The structure, composition, and function of each of the cisternae may be different inside the Golgi stack. These different variations of Golgi cisternae are categorized into 3 groups; cis Golgi network, medial, and trans Golgi network. [2] The cis Golgi network is the first step in the cisternal structure of a protein being packaged, while the trans Golgi network is the last step in the cisternal structure when the vesicle is being transferred to either the lysosome, the cell surface or the secretory vesicle. The cisternae are shaped by the cytoskeleton of the cell through a lipid bilayer. [4] Post-translational modifications such as glycosylation, phosphorylation and cleavage occur in the Golgi and as proteins travel through it, they go through the cisternae, which allows functional ion channels to be created due to these modifications. [5] Each class of cisternae contains various enzymes used in protein modifications. [2] These enzymes help the Golgi in glycosylation and phosphorylation of proteins, as well as mediate signal modifications to direct proteins to their final destination. [2] Defects in the cisternal enzymes can cause congenital defects including some forms of muscular dystrophy, cystic fibrosis, cancer, and diabetes. [2]

The trans-Golgi network is an important part of the Golgi. It is located on the trans face of the Golgi apparatus and is made up of cisternae. The cisternae play a crucial role in the packaging, modification, and transport functions for the cell overall. The proteins and polysaccharides that get processed here within the cisterna will then be sent to their specified locations. [3]

There are multiple types of cisternae which can be recognized from their distinctions in morphology. These distinctions include enzymes relating to glycosylation that have been identified in cisternae located in different regions of the Golgi. This difference in the localization of enzymes throughout cisternae can contribute to the functioning of the Golgi by regulating the pH, ion concentrations, and the amounts of substrate that are necessary. This also works to make sure that reactions are happening in the correct places within the Golgi and that proteins do not undergo the wrong modification if they are in the wrong location. [3]

This illustration shows where the cisternae can be found on the Golgi apparatus. As well as the location of the cis and trans Golgi network. Golgi apparatus (editors version).svg
This illustration shows where the cisternae can be found on the Golgi apparatus. As well as the location of the cis and trans Golgi network.

The cis Golgi network is the first step in the cisternal structure of a protein being packaged, while the trans Golgi network is the last step in the cisternal structure when the vesicle is being transferred to either the lysosome, the cell surface or the secretory vesicle. The medial cisternae is where the mannose residue and extra N-acetylglucosamine is removed.

Golgi Glycosylation

The Golgi apparatus plays a critical role in the modification of proteins through glycosylation, particularly N-linked glycosylation, which is a crucial process for the proper folding, stability, and function of many secretory and membrane-bound proteins [6] . N-linked glycosylation involves the attachment of oligosaccharides to the nitrogen atom of asparagine residues in proteins. These oligosaccharides are composed of various sugar units, including N-acetylglucosamine (GlcNAc), mannose (Man), galactose (Gal), and N-acetylneuraminate (NANA, also known as sialic acid). These glycosylated structures are integral for proper protein function, influencing cellular interactions, protein trafficking, and immune recognition [7] .

N-linked glycosylation begins in the rough endoplasmic reticulum (ER), where a precursor oligosaccharide is synthesized on a lipid carrier called dolichol. The precursor consists of a core structure made up of two N-acetylglucosamine (GlcNAc) residues, nine mannose (Man) residues, and three glucose (Glc) residues [7] . The precursor is then transferred to a protein's asparagine residue as soon as the protein enters the ER lumen. The attachment of the oligosaccharide to the asparagine is catalyzed by the enzyme oligosaccharyltransferase [8] .

Once the glycosylated protein enters the ER, further processing of the oligosaccharide occurs. Three specific enzymes play key roles in this early stage of glycosylation. First, glucosidase I removes one glucose residue from the oligosaccharide. Then, glucosidase II removes two more glucose residues, leaving behind a core oligosaccharide attached to the protein. Finally, a mannosidase enzyme removes one mannose residue [7] . After this initial trimming, the oligosaccharide is ready to move from the ER to the Golgi apparatus for more elaborate modifications.

In the Golgi, further trimming and addition of sugar residues occur, particularly the removal of mannose and the addition of various sugars such as GlcNAc, galactose (Gal), and sialic acid (NANA). Golgi mannosidase I and mannosidase II remove additional mannose residues from the oligosaccharide, further refining its structure. GlcNAc transferase then adds GlcNAc residues to the growing oligosaccharide chain by transferring GlcNAc from UDP-GlcNAc. In the medial-Golgi, the oligosaccharide undergoes more modifications, including the addition of two GlcNAc units, three Gal residues, and finally three sialic acid (NANA) residues in the trans-Golgi network [7] .

Each compartment of the Golgi plays a distinct role in glycosylation and protein processing. The cis-Golgi network is involved in the phosphorylation of oligosaccharides on lysosomal proteins, a modification that helps target proteins to the lysosomes. The medial-Golgi is the site of important reactions like the trimming of mannose and the addition of GlcNAc, which is essential for the formation of complex glycan structures. In the trans-Golgi, galactose is added to the oligosaccharide, further refining the glycan structure. The trans-Golgi network is responsible for adding sialic acid (NANA) and sorting proteins into vesicles destined for lysosomes or secretion [7] . These specialized modifications and sorting are crucial for protein functionality and their subsequent cellular destinations.

The organization of the Golgi compartments into cisternae—stacks of membrane-bound structures—ensures that enzymes are properly localized to each region, facilitating the sequential and highly regulated modification of oligosaccharides. The Golgi apparatus plays a pivotal role in N-linked glycosylation, a process that begins in the ER and is elaborated within the Golgi. Through the sequential trimming and addition of sugars like GlcNAc, mannose, galactose, and sialic acid, the Golgi ensures that proteins are properly modified for their final functional roles. The distinct regions of the Golgi, from the cis-Golgi to the trans-Golgi network, work in concert to facilitate the precise modification and sorting of glycoproteins, which are essential for a wide range of cellular functions.

Secretory Pathway

The secretory pathway is essential for the sorting, packing, and delivery of proteins to their correct cellular destinations. It begins in the rough endoplasmic reticulum (ER), where proteins are synthesized and initially sorted into vesicles for transport. These vesicles then move to the Golgi apparatus, where they undergo further processing and are directed to their final destinations, such as the plasma membrane, endosomes, or lysosomes.

The first step in the secretory pathway is the formation of transport vesicles at the ER. These vesicles are coated with COPII, a protein complex essential for budding from the ER. COPII coats consist of the small GTP-binding protein Sar1 and two additional complexes: Sec23/Sec24 and Sec13/Sec31. These coat proteins interact with membrane cargo proteins, ensuring that the right proteins are packaged into vesicles. The vesicles then move toward the cis-Golgi network, where they enter via COPII-mediated transport [7] .

The secretory pathway also requires retrograde transport to maintain cellular function. Many ER-resident proteins have specific sorting signals that direct them to be retained in the ER or returned from the Golgi if missorted. This is achieved by COPI-coated vesicles, which transport these proteins back to the ER from the Golgi in a process called retrograde trafficking. COPI vesicles also play a key role in the movement of Golgi-resident enzymes between different Golgi compartments, ensuring that each compartment maintains the necessary enzymes for proper modification of cargo proteins [7] .

Once vesicles reach the Golgi, they undergo further modifications, including glycosylation and proteolytic processing [7] . Cargo proteins move through the Golgi compartments (cis, medial, and trans) by either vesicular transport or cisternal maturation. Vesicular transport suggests that the Golgi cisternae remain static while vesicles transport cargo between compartments. In contrast, cisternal maturation poses that the Golgi cisternae themselves mature as enzymes and cargo are progressively moved through the stack, while the cisternae retrogradely exchange enzymes by COPI vesicles [6] .

At the trans-Golgi network, cargo proteins are sorted into different vesicles for delivery to their final destinations. For lysosomal proteins, a crucial modification occurs: the addition of mannose-6-phosphate (M6P) residues in the cis-Golgi. These M6P tags are recognized by M6P receptors in the trans-Golgi membrane, which directs the proteins toward late endosomes. In the endosomes, the M6P receptors dissociate from the cargo, and the receptors are recycled back to the Golgi or plasma membrane. The lysosomal enzymes are then delivered to the lysosomes for their final role in cellular degradation [7] .

Thus, the secretory pathway is a highly coordinated process, involving various vesicular transport mechanisms and modifications, to ensure that proteins are correctly sorted, processed, and delivered to their appropriate cellular locations.

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that processes proteins

The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">Endomembrane system</span> Membranes in the cytoplasm of a eukaryotic cell

The endomembrane system is composed of the different membranes (endomembranes) that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, vesicles, endosomes, and plasma (cell) membrane among others. The system is defined more accurately as the set of membranes that forms a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport. Importantly, the endomembrane system does not include the membranes of plastids or mitochondria, but might have evolved partially from the actions of the latter.

<span class="mw-page-title-main">Golgi apparatus</span> Cell organelle that packages proteins for export

The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. 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.

<span class="mw-page-title-main">Glycoprotein</span> Protein with oligosaccharide modifications

Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

A congenital disorder of glycosylation is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants. The most common sub-type is PMM2-CDG where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

<span class="mw-page-title-main">Mannose</span> Chemical compound

Mannose is a sugar with the formula HOCH2(CHOH)4CHO. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation are associated with mutations in enzymes involved in mannose metabolism.

Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule in order to form a glycoconjugate. In biology, glycosylation usually refers to an enzyme-catalysed reaction, whereas glycation may refer to a non-enzymatic reaction.

<span class="mw-page-title-main">Hemagglutinin esterase</span> Glycoprotein present in some enveloped viruses

Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C virus, toroviruses, and coronaviruses of the subgenus Embecovirus. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.

<span class="mw-page-title-main">Oligosaccharyltransferase</span> Class of enzymes

Oligosaccharyltransferase or OST (EC 2.4.1.119) is a membrane protein complex that transfers a 14-sugar oligosaccharide from dolichol to nascent protein. It is a type of glycosyltransferase. The sugar Glc3Man9GlcNAc2 (where Glc=Glucose, Man=Mannose, and GlcNAc=N-acetylglucosamine) is attached to an asparagine (Asn) residue in the sequence Asn-X-Ser or Asn-X-Thr where X is any amino acid except proline. This sequence is called a glycosylation sequon. The reaction catalyzed by OST is the central step in the N-linked glycosylation pathway.

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II, is part of the lysosomal storage disease family and results from a defective phosphotransferase. This enzyme transfers phosphate to mannose residues on specific proteins. Mannose-6-phosphate serves as a marker for proteins to be targeted to lysosomes within the cell. Without this marker, proteins are instead secreted outside the cell, which is the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances in various tissues throughout the body. As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells" seen microscopically. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood, but they remain inactive at blood pH because they require the low lysosomal pH 5 to function.

<span class="mw-page-title-main">Insulin-like growth factor 2 receptor</span> Protein found in humans

Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.

<span class="mw-page-title-main">Mannose 6-phosphate</span> Chemical compound

Mannose-6-phosphate (M6P) is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase.

The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates.

<span class="mw-page-title-main">Mannose phosphate isomerase</span>

Mannose-6 phosphate isomerase (MPI), alternately phosphomannose isomerase (PMI) is an enzyme which facilitates the interconversion of fructose 6-phosphate (F6P) and mannose-6-phosphate (M6P). Mannose-6-phosphate isomerase may also enable the synthesis of GDP-mannose in eukaryotic organisms. M6P can be converted to F6P by mannose-6-phosphate isomerase and subsequently utilized in several metabolic pathways including glycolysis and capsular polysaccharide biosynthesis. PMI is monomeric and metallodependent on zinc as a cofactor ligand. PMI is inhibited by erythrose 4-phosphate, mannitol 1-phosphate, and to a lesser extent, the alpha anomer of M6P.

The enzyme mannosyl-glycoprotein endo-β-N-acetylglucosaminidase (endoglycosidase H) (EC 3.2.1.96) has systematic name glycopeptide-D-mannosyl-N4-(N-acetyl-D-glucosaminyl)2-asparagine 1,4-N-acetyl-β-glucosaminohydrolase. It is a highly specific endoglycosidase which cleaves asparagine-linked mannose rich oligosaccharides, but not highly processed complex oligosaccharides from glycoproteins. It is used for research purposes to deglycosylate glycoproteins and to monitor intracellular protein trafficking through the secretory pathway.

N-acetylglucosamine-1-phosphate transferase (GlcNAc-1-phosphotransferase) is a transferase enzyme.

<i>N</i>-linked glycosylation Attachment of an oligosaccharide to a nitrogen atom

N-linked glycosylation is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom, in a process called N-glycosylation, studied in biochemistry. The resulting protein is called an N-linked glycan, or simply an N-glycan.

Wrinkly skin syndrome(WSS) is a rare genetic condition characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanelle (soft spot) closure, along with a range of other symptoms. The disorder exhibits an autosomal recessive inheritance pattern with mutations in the ATP6V0A2 gene, leading to abnormal glycosylation events. There are only about 30 known cases of WSS as of 2010. Given its rarity and symptom overlap with other dermatological conditions, reaching an accurate diagnosis is difficult and requires specialized dermatological testing. Limited treatment options are available but long-term prognosis is variable from patient to patient, based on individual case studies. Some skin symptoms recede with increasing age, while progressive neurological advancement of the disorder causes seizures and mental deterioration later in life for some patients.

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.

<span class="mw-page-title-main">GNPTG</span> Protein-coding gene in the species Homo sapiens

GNPTG is a gene in the human body. It is one of three genes that were found to correlate with stuttering.

References

  1. ↑ Robert Hine, ed. (2019). A dictionary of biology (Eighth ed.). Oxford. ISBN   978-0-19-186081-2. OCLC   1100041140.{{cite book}}: CS1 maint: location missing publisher (link)
  2. 1 2 3 4 5 6 7 "Golgi Apparatus, Proteins, Transport". Scitable. Retrieved 2021-05-07.
  3. 1 2 3 Day, Kasey J.; Staehelin, L. Andrew; Glick, Benjamin S. (2013-07-24). "A three-stage model of Golgi structure and function". Histochemistry and Cell Biology. 140 (3): 239–249. doi:10.1007/s00418-013-1128-3. ISSN   0948-6143. PMC   3779436 . PMID   23881164.
  4. ↑ Luini, A.; Parashuraman, S. (2016), "Golgi and TGN", Golgi and TGN, Encyclopedia of Cell Biology, Elsevier, pp. 183–191, doi:10.1016/b978-0-12-394447-4.20014-x, ISBN   978-0-12-394796-3
  5. ↑ Geoffrey S. Pitt, ed. (2016). Ion Channels in Health and Disease. doi:10.1016/c2014-0-01711-x. ISBN   9780128020029.
  6. 1 2 Liu, Jianyang; Huang, Yan; Li, Ting; Jiang, Zheng; Zeng, Liuwang; Hu, Zhiping (2021-04-01). "The role of the Golgi apparatus in disease (Review)". International Journal of Molecular Medicine. 47 (4): 1. doi:10.3892/ijmm.2021.4871. ISSN   1107-3756. PMC   7891830 . PMID   33537825.
  7. 1 2 3 4 5 6 7 8 9 Lodish, Harvey F. (2016). Molecular cell biology (Eighth edition ed.). New York: W. H. Freeman-Macmillan Learning. ISBN   978-1-4641-8339-3.
  8. ↑ Mohanty, Smita; P Chaudhary, Bharat; Zoetewey, David (2020). "Structural Insight into the Mechanism of N-Linked Glycosylation by Oligosaccharyltransferase". Biomolecules. 10 (4): 624. doi: 10.3390/biom10040624 . ISSN   2218-273X. PMC   7226087 . PMID   32316603.


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