The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division. The MTOC is a major site of microtubule nucleation and can be visualized in cells by immunohistochemical detection of γ-tubulin. The morphological characteristics of MTOCs vary between the different phyla and kingdoms. [1] In animals, the two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation.
Microtubule-organizing centers function as the site where microtubule formation begins, as well as a location where free-ends of microtubules attract to. [2] Within the cells, microtubule-organizing centers can take on many different forms. An array of microtubules can arrange themselves in a pinwheel structure to form the basal bodies, which can lead to the formation of microtubule arrays in the cytoplasm or the 9+2 axoneme. Other arrangements range from fungi spindle pole bodies to the eukaryotic chromosomal kinetochores (flat, laminated plaques). MTOCs can be freely dispersed throughout the cytoplasm or centrally localized as foci. The most notable MTOCs are the centrosome at interphase and the mitotic spindle poles.
Centrioles can act as markers for MTOCs in the cell. [2] If they are freely distributed in the cytoplasm, centrioles can gather during differentiation to become MTOCs. They can also be focused around a centrosome as a single MTOC, though centrosomes can work as an MTOC absent of centrioles.
Most animal cells have one MTOC during interphase, usually located near the nucleus, and generally associated closely with the Golgi apparatus. The MTOC is made up of a pair of centrioles at its center, and is surrounded by pericentriolar material (PCM) that is important for microtubule nucleation. Microtubules are anchored at the MTOC by their minus ends, while their plus ends continue to grow into the cell periphery. The polarity of the microtubules is important for cellular transport, as the motor proteins kinesin and dynein typically move preferentially in the "plus" and "minus" directions respectively, along a microtubule, allowing vesicles to be directed to or from the endoplasmic reticulum and Golgi apparatus. Particularly for the Golgi apparatus, structures associated with the apparatus travel towards the minus end of a microtubule and aid in the overall structure and site of the Golgi in the cell. [3]
Movements of the microtubules are based on the actions of the centrosome. [1] Each daughter cell after the cessation of mitosis contains one primary MTOC. [2] Before cell division begins, the interphase MTOC replicates to form two distinct MTOCs (now typically referred to as centrosomes). During cell division, these centrosomes move to opposite ends of the cell and nucleate microtubules to help form the mitotic/meiotic spindle. If the MTOC does not replicate, the spindle cannot form, and mitosis ceases prematurely. [1]
γ-tubulin is a protein located at the centrosome that nucleates the microtubules by interacting with the tubulin monomer subunit in the microtubule at the minus end. [1] Organization of the microtubules at the MTOC, or centrosome in this case, is determined by the polarity of the microtubules defined by y-tubulin. [1]
In epithelial cells, MTOCs also anchor and organize the microtubules that make up cilia. As with the centrosome, these MTOCs stabilize and give direction to the microtubules, in this case to allow unidirectional movement of the cilium itself, rather than vesicles moving along it.
In yeasts and some algae, the MTOC is embedded into the nuclear envelope as a spindle pole body. Centrioles do not exist in the MTOCs of yeast and fungi. [1] In these organisms, the nuclear envelope does not break down during mitosis and the spindle pole body serves to connect cytoplasmic with nuclear microtubules. The disc-shaped spindle pole body is organized into three layers: the central plaque, inner plaque, and outer plaque. The central plaque is embedded in the membrane, while the inner plaque is an amorphous intranuclear layer, and the outer plaque is the layer located in the cytoplasm. [1]
Plant cells lack centrioles or spindle pole bodies except in their flagellate male gametes, and they are entirely absent in the conifers and flowering plants. [4] Instead, the nuclear envelope itself appears to function as the main MTOC for microtubule nucleation and spindle organization during plant cell mitosis.
The MTOC reorients itself during signal transduction, primarily during wound repair or immune responses. [5] The MTOC is relocalized to a position between the edge of the cell and the nucleus in cells like macrophages, fibroblasts, and endothelial cells. Organelles like the Golgi apparatus aid in the reorientation of the MTOC which can occur rapidly. Transduction signals cause microtubules to grow or contract, as well as cause the centrosome to become motile. The MTOC is located in a perinuclear position and contains the negative ends of microtubules while the positive ends grow rapidly towards the edge of the cell. The Golgi apparatus reorients along with the MTOC, and together cause the cell to seemingly send a polarized signal. [5]
In immune responses, upon interaction with a target cell in response to antigen-specific loaded antigen-presenting cells, immune cells, such as the T cells, natural killer cells, and cytotoxic T lymphocytes, localize their MTOCs near the contact zone between the immune cell and the target cell. For T cells, the T cell receptor signaling response causes the reorientation of the MTOC by microtubules shortening to bring the MTOC to the site of interaction of the T cell receptor. [5]
In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and are only present in the male gametes of charophytes, bryophytes, seedless vascular plants, cycads, and Ginkgo. A bound pair of centrioles, surrounded by a highly ordered mass of dense material, called the pericentriolar material (PCM), makes up a structure called a centrosome.
Mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the total number of chromosomes is maintained. Mitosis is preceded by the S phase of interphase and is followed by telophase and cytokinesis, which divide the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic phase of a cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.
Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.
In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.
A basal body is a protein structure found at the base of a eukaryotic undulipodium. The basal body was named by Theodor Wilhelm Engelmann in 1880. It is formed from a centriole and several additional protein structures, and is, essentially, a modified centriole. The basal body serves as a nucleation site for the growth of the axoneme microtubules. Centrioles, from which basal bodies are derived, act as anchoring sites for proteins that in turn anchor microtubules, and are known as the microtubule organizing center (MTOC). These microtubules provide structure and facilitate movement of vesicles and organelles within many eukaryotic cells.
Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.
Katanin is a microtubule-severing AAA protein. It is named after the Japanese sword called a katana. Katanin is a heterodimeric protein first discovered in sea urchins. It contains a 60 kDa ATPase subunit, encoded by KATNA1, which functions to sever microtubules. This subunit requires ATP and the presence of microtubules for activation. The second 80 kDA subunit, encoded by KATNB1, regulates the activity of the ATPase and localizes the protein to centrosomes. Electron microscopy shows that katanin forms 14–16 nm rings in its active oligomerized state on the walls of microtubules.
In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, strength, and rigidity to the cell. When the filaments are packed up together, they are able to form three different cellular parts. The three major classes of protein filaments that make up the cytoskeleton include: actin filaments, microtubules and intermediate filaments.
The spindle pole body (SPB) is the microtubule organizing center in yeast cells, functionally equivalent to the centrosome. Unlike the centrosome the SPB does not contain centrioles. The SPB organises the microtubule cytoskeleton which plays many roles in the cell. It is important for organising the spindle and thus in cell division.
Preprophase is an additional phase during mitosis in plant cells that does not occur in other eukaryotes such as animals or fungi. It precedes prophase and is characterized by two distinct events:
In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.
Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.
An aster is a cellular structure shaped like a star, consisting of a centrosome and its associated microtubules during the early stages of mitosis in an animal cell. Asters do not form during mitosis in plants. Astral rays, composed of microtubules, radiate from the centrosphere and look like a cloud. Astral rays are one variant of microtubule which comes out of the centrosome; others include kinetochore microtubules and polar microtubules.
Centrosomes are the major microtubule organizing centers (MTOC) in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. A centrosome is composed of two orthogonal cylindrical protein assemblies, called centrioles, which are surrounded by a protein dense amorphous cloud of pericentriolar material (PCM). The PCM is essential for nucleation and organization of microtubules. The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle progresses, the centrosome undergoes a series of morphological and functional changes. Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs.
Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) is a protein in humans that is encoded by the CAMSAP2 gene. CAMSAP2 possesses a microtubule-binding domain near the C-terminal region where "microtubule interactions" occur. On the C-terminal regions, protein to protein interactions are accelerated by three coiled-coil domains, which function as molecular spacers. CAMSAP2 acts as a microtubule minus-end anchor and binds microtubules through its CKK domain. CAMSAP2 is necessary for the proper organization and stabilization of interphase microtubules. The protein also plays a role in cell migration. CAMSAP2 stabilizes and attaches microtubule minus ends to the Golgi through the AKAP9 complex and myomegalin. CLASP1 proteins are responsible for microtubule stability which are not required for the Golgi tethering. When no centromeres are present, AKAP9 and CAMSAP-2 dependent pathways of the microtubule minus ends become a dominant force and must exist in order to observe the maintenance of microtubule density.
J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.
Holomastigotoides is a genus of parabasalids found in the hindgut of lower termites. It is characterized by its dense, organized arrangement of flagella on the cell surface and the presence of a mitotic spindle outside its nucleus during the majority of its cell cycle. As a symbiont of termites, Holomastigotoides is able to ingest wood and aid its host in digestion. In return, Holomastigotoides is supplied with a stable habitat and steady supply of food. Holomastigotoides has notably been studied to observe the mechanisms of chromosomal pairing and segregation in haploid and diploid cells.
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