Granule (cell biology)

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In cell biology, a granule is a small particle barely visible by light microscopy. The term is most often used to describe a secretory vesicle containing important components of cell phyisology. [1] Examples of granules include granulocytes, platelet granules, insulin granules, germane granules, starch granules, and stress granules.

Contents

Granules in Leukocytes

A group of leukocytes, called granulocytes, are white blood cells containing enzyme granules that play a significant role in the immune system. Granulocytes include neutrophils, eosinophils, and basophils which attack bacteria or parasites, and respond to allergens. Each type of granulocyte contains enzymes and chemicals tailored to it’s function. [2]

Neutrophils for example, contain primary granules, secondary granules, tertiary granules, and secretory vesicles. Primary vesicles, also known as azurophilic granules, secrete hydrolytic enzymes including Including elastase, myeloperoxidase, cathepsins, and defensins that aid in pathogen distruction. Secondary granules, or specific granules, in neutrophils contain iron-binding protein lactoferrin. Tertiary granules contain matrix metalloproteinases. [3] [4]

Other immune cells, such as natural killer cells, contain granular enzymes, including perforin and proteases which can lead to the lysis of neighboring cells. [3]  

The process by which granule contents are released is known as degranulation. This tightly controlled process is initiated by immunological stimuli and results in the movement of granules to the cell membrane for fusion and release. [3]

Granules in Platelets

The granules of platelets are classified as dense granules and alpha granules.

α-Granules are unique to platelets and are the most abundant of the platelet granules, numbering 50–80 per platelet 2. These granules measure 200–500 nm in diameter and account for about 10% of platelet volume. They contain mainly proteins, both membrane-associated receptors (for example, αIIbβ3 and P-selectin) and soluble cargo (for example, platelet factor 4 [PF4] and fibrinogen). Proteomic studies have identified more than 300 soluble proteins that are involved in a wide variety of functions, including hemostasis (for example, von Willebrand factor [VWF] and factor V), inflammation (for example, chemokines such as CXCL1 and interleukin-8), and wound healing (for example, vascular endothelial growth factor [VEGF] and fibroblast growth factor [FGF]) 3. The classic representation of α-granules as spherical organelles with a peripheral limiting membrane, a dense nucleoid, and progressively lucent peripheral zones on transmission electron microscopy is probably simplistic and may be in part a preparation artifact. Electron tomography with three-dimensional reconstruction of platelets is notable for a significant percentage of tubular α-granules that generally lack VWF 4. More recent work using transmission electron microscopy and freeze substitution dehydration of resting platelets shows that α-granules are ovoid with a generally homogeneous matrix and that tubes form from α-granules upon activation 5. Thus, whether or not there exists significant structural heterogeneity among α-granules remains to be completely resolved. α-Granule exocytosis is evaluated primarily by plasma membrane expression of P-selectin (CD62P) by flow cytometry or estimation of the release of PF4, VWF, or other granule cargos. [5]

Dense granules (also known as δ-granules) are the second most abundant platelet granules, with 3–8 per platelet. They measure about 150 nm in diameter 2. These granules, unique to the platelets, are a subtype of lysosome-related organelles (LROs), a group that also includes melanosomes, lamellar bodies of the type II alveolar cells, and lytic granules of cytotoxic T cells. Dense granules mainly contain bioactive amines (for example, serotonin and histamine), adenine nucleotides, polyphosphates, and pyrophosphates as well as high concentrations of cations, particularly calcium. These granules derive their name from their electron-dense appearance on whole mount electron microscopy, which results from their high cation concentrations . Dense granule exocytosis is typically evaluated by ADP/ATP release by using luciferase-based luminescence techniques, release of preloaded [ 3H] serotonin, or membrane expression of lysosome-associated membrane protein 2 (LAMP2) or CD63 by flow cytometry. [5]

Other platelet granules have been described. Platelets contain about 1–3 lysosomes per platelet and peroxisomes, the platelet-specific function of which remains unclear. Lysosomal exocytosis is typically evaluated by estimation of released lysosomal enzymes such as beta hexosaminidase. An electron-dense granule defined by the presence of Toll-like receptor 9 (TLR9) and protein disulfide isomerase (PDI), termed the T granule, has also been described, although its existence remains controversial. PDI and other platelet-borne thiol isomerases have been reported to be packaged within a non-granular compartment derived from the megakaryocyte endoplasmic reticulum (ER), which may be associated with the dense tubular system. [5]

Insulin Granules in Beta Cells

Beta cell with insulin granules, which are the dark black spots surrounded by a white area called a halo. Beta cell processed.jpg
Beta cell with insulin granules, which are the dark black spots surrounded by a white area called a halo.

Insulin granules are a specific type of granule found in pancreatic beta cells. Insulin granules are secretory granules, which are responsible for the storage and secretion of insulin, a hormone that regulates the concentration of glucose in the bloodstream to maintain homeostasis. The release of insulin by granules is signaled by plasma glucose concentrations and the resultant influx of calcium ions in pancreatic cells, which initiate granule exocytosis. Insulin release is biphastic, as insulin is first released in the primary phase by granules closest to the plasma membrane. In the secondary phase, insulin granules are recruited from reserves deeper in the beta cell for a slower release rate. [6]

Insulin granules undergo a significant maturation process. First, precursor proinsulin molecules are synthesized in the endoplasmic reticulum and packaged in the golgi network. Insulin granules bud from the trans golgi network and are further sorted via clathrin-coated vesicle transport. After budding, insulin secretory granules are acidified, activating endoproteases PC1/3 and PC2 to convert proinsulin into insulin. The clatherin coating is released and the insulin secretory granules are transported across the cell via actin filaments and microtubules. [7]

Germline granules

In 1957, André and Rouiller first coined the term "nuage". [8] (French for "cloud"). Its amorphous and fibrous structure occurred in drawings as early as in 1933 (Risley). Today, the nuage is accepted to represent a characteristic, electrondense germ plasm organelle encapsulating the cytoplasmic face of the nuclear envelope of the cells destined to the germline fate. The same granular material is also known under various synonyms: dense bodies, mitochondrial clouds, yolk nuclei, Balbiani bodies, perinuclear P granules in Caenorhabditis elegans, germinal granules in Xenopus laevis, chromatoid bodies in mice, and polar granules in Drosophila . Molecularly, the nuage is a tightly interwoven network of differentially localized RNA-binding proteins, which in turn localize specific mRNA species for differential storage, asymmetric segregation (as needed for asymmetric cell division), differential splicing and/or translational control. The germline granules appear to be ancestral and universally conserved in the germlines of all metazoan phyla.

Many germline granule components are part of the piRNA pathway and function to repress transposable elements.

Starch Granules in Plants

Starch is an insoluble carbohydrate used for energy storage in plant cells. There are two forms of starch, transitionary starch and storage starch. Transitionary starch is synthesised via photosynthesis and found in photosythetic plant tissue cells, such as the leaves. Storage starch is reserved for longer periods of time and is found in non-photosynthetic tissue cells such as the roots or stem. Storage starch is utilized during germination or regrowth, or when energy demands exceed net energy production from photosynthesis. [9]

Starch granules in potato cells. Starch granules of potato02.jpg
Starch granules in potato cells.

Starch is stored in granule form. Starch granules are composed of a crystalline structure of amylopectin and amylose. Amylopectin forms the structure of the starch granule, with branching and non branching A-chains, B-chains, and C-chains. Amylose fills in the gaps of the amylopectin structure. Under a microscope, starch granules look like concentric layers, referred to as “growth rings”. Starch granules also contain granule-bound starch synthase and amylopectin synthesizing enzymes. Notably, starch granules vary in size and morphology across plant tissues and species. [10]

Stress Granules

Stress granules are composed of protein and RNA, and form from pools of mRNAs that have not started translation as a result of environmental conditions including oxidative stress, temperature, toxins, and osmotic pressure. Stress granules also contain translation initiation factors, RNA binding proteins (which account for 50% of the granule’s components), and non-RNA binding proteins. They are formed via protein-protein interactions between mRNA binding proteins and are influenced by protein methylation or phosphorylation. They contain a “core” with high concentrations of proteins and mRNA and a less-concentrated outer region. Stress granules are dynamic in structure, and can dock and exchange with p-bodies or the cytoplasm. They can also perform fusion and fission in the cytoplasm. [11]

Assembly and disassembly of stress granules. Stress granule dynamics.png
Assembly and disassembly of stress granules.

Stress granule assembly is dependent upon the conditions of the cell. In yeast, stress granules form under conditions of high heat. Stress granules are of significance for their roles in mRNA localization, cell signaling pathways, and antiviral processes. Once disassembled, the RNA inside stress granules can go back to translation or be removed as cellular waste. Stress granules may provide protection for mRNA from interactions with the cytosol. Moreover, mutations that affect the formation or degradation of stress granules may contribute to neurodegenerative conditions such as ALS and FTLD. However, the effects of stress granules on cell physiology are still under study. [12]

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and 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">Vesicle (biology and chemistry)</span> Any small, fluid-filled, spherical organelle enclosed by a membrane

In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, the vesicles are called unilamellar liposomes; otherwise they are called multilamellar liposomes. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.

<span class="mw-page-title-main">Exocytosis</span> Active transport and bulk transport in which a cell transports molecules out of the cell

Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a component of blood whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

Weibel–Palade bodies (WPBs) are the storage granules of endothelial cells, the cells that form the inner lining of the blood vessels and heart. They manufacture, store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in hemostasis and inflammation.

<span class="mw-page-title-main">Rhoptry</span>

A rhoptry is a specialized secretory organelle. They are club-shaped organelles connected by thin necks to the extreme apical pole of the parasite. These organelles, like micronemes, are characteristic of the motile stages of Apicomplexa protozoans. They can vary in number and shape and contain numerous enzymes that are released during the process of host penetration. The proteins they contain are important in the interaction between the host and the parasite, including the formation of the parasitophorous vacuole (PV).

<span class="mw-page-title-main">Dense granule</span>

Dense granules are specialized secretory organelles. Dense granules are found only in platelets and are smaller than alpha granules. The origin of these dense granules is still unknown, however, it is thought that may come from the mechanism involving the endocytotic pathway. Dense granules are a sub group of lysosome-related organelles (LRO). There are about three to eight of these in a normal human platelet.

<span class="mw-page-title-main">Endoplasm</span> Also known as entoplasm

Endoplasm generally refers to the inner, dense part of a cell's cytoplasm. This is opposed to the ectoplasm which is the outer (non-granulated) layer of the cytoplasm, which is typically watery and immediately adjacent to the plasma membrane. The nucleus is separated from the endoplasm by the nuclear envelope. The different makeups/viscosities of the endoplasm and ectoplasm contribute to the amoeba's locomotion through the formation of a pseudopod. However, other types of cells have cytoplasm divided into endo- and ectoplasm. The endoplasm, along with its granules, contains water, nucleic acids, amino acids, carbohydrates, inorganic ions, lipids, enzymes, and other molecular compounds. It is the site of most cellular processes as it houses the organelles that make up the endomembrane system, as well as those that stand alone. The endoplasm is necessary for most metabolic activities, including cell division.

<span class="mw-page-title-main">P-selectin</span> Type-1 transmembrane protein

P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.

A secretory protein is any protein, whether it be endocrine or exocrine, which is secreted by a cell. Secretory proteins include many hormones, enzymes, toxins, and antimicrobial peptides. Secretory proteins are synthesized in the endoplasmic reticulum.

<span class="mw-page-title-main">Alpha granule</span> Cellular component of platelets

Alpha granules, (α-granules) also known as platelet alpha-granules are a cellular component of platelets. Platelets contain different types of granules that perform different functions, and include alpha granules, dense granules, and lysosomes. Of these, alpha granules are the most common, making up 50% to 80% of the secretory granules. Alpha granules contain several growth factors.

Specific granules are secretory vesicles found exclusively in cells of the immune system called granulocytes.

<span class="mw-page-title-main">Degranulation</span> Process by which cells lose secretory granules

Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulocytes. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms.

<span class="mw-page-title-main">STX4</span> Protein-coding gene in the species Homo sapiens

Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.

<span class="mw-page-title-main">VAMP2</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones.

Kiss-and-run fusion is a type of synaptic vesicle release where the vesicle opens and closes transiently. In this form of exocytosis, the vesicle docks and transiently fuses at the presynaptic membrane and releases its neurotransmitters across the synapse, after which the vesicle can then be reused.

Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory cell. It takes place in the form of Golgi membrane-bound micro-sized vesicles, termed membrane vesicles (MVs).

<span class="mw-page-title-main">Outer membrane vesicle</span> Vesicles released from the outer membranes of Gram-negative bacteria

Outer membrane vesicles (OMVs) are vesicles released from the outer membranes of Gram-negative bacteria. While Gram-positive bacteria release vesicles as well those vesicles fall under the broader category of bacterial membrane vesicles (MVs). OMVs were the first MVs to be discovered, and are distinguished from outer inner membrane vesicles (OIMVS), which are gram-negative baterial vesicles containing portions of both the outer and inner bacterial membrane. Outer membrane vesicles were first discovered and characterized using transmission-electron microscopy by Indian Scientist Prof. Smriti Narayan Chatterjee and J. Das in 1966-67. OMVs are ascribed the functionality to provide a manner to communicate among themselves, with other microorganisms in their environment and with the host. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins and allied virulence molecules. This communication happens in microbial cultures in oceans, inside animals, plants and even inside the human body.

In cellular biology, a chromatoid body is a dense structure in the cytoplasm of male germ cells. It is composed mainly of RNA and RNA-binding proteins and is thus a type of RNP granule. Chromatoid body-like granules first appear in spermatocytes and condense into a single granule in round spermatids. The structure disappears again when spermatids start to elongate. The chromatoid body is crucial for spermatogenesis, but its exact role in the process is not known. Following significant strides in the understanding of small non-coding RNA mediated gene regulation and Piwi-interacting RNA (piRNA) and their roles in germline development, the function of chromatoid bodies (CBs) has been somewhat elucidated. However, due to similarities with RNP granules found in somatic cells – such as stress granules and processing bodies – chromatoid body is thought to be involved in post-transcriptional regulation of gene expression. Postmeiotic germ cell differentiation induces the accumulation of piRNAs and proteins of piRNA machinery along with several distinct RNA regulator proteins. Although evidence suggests CB involvement in mRNA regulation and small RNA mediated gene regulation, the mechanism of action remains obscure.

References

  1. ↑ "Granulocytes: Definition, Types & Function". Cleveland Clinic. Retrieved 2024-03-25.
  2. ↑ "Granulocytes: Definition, Types & Function". Cleveland Clinic. Retrieved 2024-03-25.
  3. 1 2 3 Lacy, Paige (September 2006). "Mechanisms of Degranulation in Neutrophils". Allergy, Asthma & Clinical Immunology. 2 (3): 98–108. doi: 10.1186/1710-1492-2-3-98 . ISSN   1710-1492. PMC   2876182 . PMID   20525154.
  4. ↑ Nordenfelt, Pontus; Winberg, Martin E.; Lönnbro, Per; Rasmusson, Birgitta; Tapper, Hans (December 2009). "Different Requirements for Early and Late Phases of Azurophilic Granule–Phagosome Fusion". Traffic. 10 (12): 1881–1893. doi:10.1111/j.1600-0854.2009.00986.x. ISSN   1398-9219. PMID   19804565.
  5. 1 2 3 Sharda, Anish; Flaumenhaft, Robert (28 February 2018). "The life cycle of platelet granules". F1000Research. 7: 236. doi: 10.12688/f1000research.13283.1 . ISSN   2046-1402. PMC   5832915 . PMID   29560259. CC-BY icon.svg Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  6. ↑ Hutton, J. C. (May 1989). "The insulin secretory granule". Diabetologia. 32 (5): 271–281. doi:10.1007/BF00265542. ISSN   0012-186X. PMID   2526768.
  7. ↑ Omar-Hmeadi, Muhmmad; Idevall-Hagren, Olof (March 2021). "Insulin granule biogenesis and exocytosis". Cellular and Molecular Life Sciences. 78 (5): 1957–1970. doi:10.1007/s00018-020-03688-4. ISSN   1420-682X. PMC   7966131 . PMID   33146746.
  8. ↑ André J, Rouiller CH (1957) L'ultrastructure de la membrane nucléaire des ovocytes del l'araignée (Tegenaria domestica Clark). Proc European Conf Electron Microscopy, Stockholm 1956. Academic Press, New York, pp 162 164
  9. ↑ Pfister, Barbara; Zeeman, Samuel C. (July 2016). "Formation of starch in plant cells". Cellular and Molecular Life Sciences. 73 (14): 2781–2807. doi:10.1007/s00018-016-2250-x. ISSN   1420-682X. PMC   4919380 . PMID   27166931.
  10. ↑ Pfister, Barbara; Zeeman, Samuel C. (July 2016). "Formation of starch in plant cells". Cellular and Molecular Life Sciences. 73 (14): 2781–2807. doi:10.1007/s00018-016-2250-x. ISSN   1420-682X. PMC   4919380 . PMID   27166931.
  11. ↑ Protter, David S.W.; Parker, Roy (September 2016). "Principles and Properties of Stress Granules". Trends in Cell Biology. 26 (9): 668–679. doi:10.1016/j.tcb.2016.05.004. PMC   4993645 . PMID   27289443.
  12. ↑ Protter, David S.W.; Parker, Roy (September 2016). "Principles and Properties of Stress Granules". Trends in Cell Biology. 26 (9): 668–679. doi:10.1016/j.tcb.2016.05.004. PMC   4993645 . PMID   27289443.


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