Microtubule Organizing Centers MTOC and Centrioles

MTOC and their chief components, centrioles, are the specific apparatus within living cells which trigger and guide reorganization of cytoplasm such as occurs during growth, generation of form and function ("differentiation") and cell movement. The enigmatic MTOC determine where, when, and how these functions occur (Figure 5.11).

MTOC (or "centrosomes") contain centrioles and "pericentriolar substance" which facilitates tubulin assembly by somehow lowering Cc. Centrioles are the common structure in all of these cellular control centers. Centrioles are composed of two similar cylinders; their diameters are 0.2 microns or 200 nanometers. Each cylinder possesses a 9 fold radial symmetry and is constructed essentially of 9 triplets of microtubules fused longitudinally. "Satellites," electron dense proteins, appear to orbit the centrioles. A cartwheel filamentous structure ("pinwheel") connects all the microtubules within each centriole at one end. One centriole begets another by replication perpendicular to the cylindrical surface of the centriole. The first step in cell division is maturation of the "mother" cell, followed by separation of pairs of centrioles and migration to establish architecture of "daughter" cells. Centriole mechanisms of perpendicular replication, orientation and guidance are unknown.

Figure 5.9: Microtubules in mitotic PtK2 cell labeled with tyrosine tubulin immunogold. The spindle pole region (MTOC) at left is a focus for spindle MT which radiate toward chromosomes (dark material). Insert upper right: kinetochore MT attaching chromosome. With permission from Geuens, Gundersen, Nuydens, Cornellisen, Bulinski, DeBrabander (1986).

Figure 5.9: Microtubules in mitotic PtK2 cell labeled with tyrosine tubulin immunogold. The spindle pole region (MTOC) at left is a focus for spindle MT which radiate toward chromosomes (dark material). Insert upper right: kinetochore MT attaching chromosome. With permission from Geuens, Gundersen, Nuydens, Cornellisen, Bulinski, DeBrabander (1986).

Between cell division cycles ("interphase"), the MT system is relatively quiescent and "radial." Most cell MT are anchored at one end to the MTOC, although they don't appear to contact any structures. Rather, MT minus ends are somehow stabilized by the "pericentriolar material." This favors MT assembly and protects against disassembly by binding and capping the minus end of MT. Most tubulin is polymerized during interphase, however free MT not radiating from the MTOC occur near the periphery of the cell. Except for free MT, the network is rather stable with low turnover rates and minimal treadmilling and dynamic instability.

During "prophase", the cytoskeleton prepares for the separation of duplicated chromosomes so the cell can make a copy of itself. DeBrabander (1985):

It appears that nature selected a near fail safe microtubule based mechanism to allow the eukaryotic cell to handle more and more complex genetic libraries.

Figure 5.10: DeBrabander's model of MTOC action. Upper left: A centriole is surrounded by a dense material that lowers Cc, the critical concentration of tubulin required for microtubule assembly. At the beginning of mitosis, new MT are preferentially nucleated near the MTOC. Upper right: Kinetochore plates associated with chromosomes also have the Cc lowering material but anchor plus ends; new MT form. Middle: MT minus ends are stabilized by the pericentriolar dense material and plus ends grow outward. Free MT are unstabilized and remain short due to consumption of tubulin subunits by MTOC stabilized MT. Bottom: stabilized MT slide along one another to pull chromosomes apart. With permission from Marc DeBrabander (1982).

Figure 5.10: DeBrabander's model of MTOC action. Upper left: A centriole is surrounded by a dense material that lowers Cc, the critical concentration of tubulin required for microtubule assembly. At the beginning of mitosis, new MT are preferentially nucleated near the MTOC. Upper right: Kinetochore plates associated with chromosomes also have the Cc lowering material but anchor plus ends; new MT form. Middle: MT minus ends are stabilized by the pericentriolar dense material and plus ends grow outward. Free MT are unstabilized and remain short due to consumption of tubulin subunits by MTOC stabilized MT. Bottom: stabilized MT slide along one another to pull chromosomes apart. With permission from Marc DeBrabander (1982).

Figure 5.11: Microtubules in PtK2 cells illustrated by tubulin antibody at two different magnifications. Nucleus (left) is devoid of MT, which densely emanate from nearby MTOC. With permission from Geuens, Gundersen, Nuydens, Cornellisen, Bulinski, and DeBrabander (1986).

As the chromosomes condense in prophase, the MT system changes its display and turnover rate. Interphase MT are gradually shortened while new MT start to grow from the centrosome. At this point, the system is extremely sensitive to polymerization inhibitors. Drugs which are used against cancer are often mitotic inhibitors which prevent the rapid polymerization of prophase MT from MTOC. Kinetochores are mobile MTOC which attach chromosomes and bind MT at their plus end (Figure 5.10). MT assemble between centrosomes (which bind their minus end) and kinetochores (which bind their plus end) and separate the genetic material towards the daughter cell poles in the mitotic cycle. The delicate array of the two centrioles, connected MT spindles and "star-like astral projections" (MT which "overshoot" the centrioles) have suggested to many observers some type of electromagnetic field because of the resemblance to a magnetic field pattern. The contractile ring formed perpendicular to the axis of mitosis by the microtrabecular lattice establishes a cleavage furrow which separates the daughter cells. The chromosome material decondenses while a new nuclear membrane is zipped onto it, and cellular elements assume again an organized aspect. Later, the cells flatten and gradually reassume their normal interphase shape.

Figure 5.12: Schematic representation of a microtubule associated protein (MAP dark lines) facilitating assembly of a microtubule (MT). The longitudinal binding retards dissociation of subunits and stabilizes the MT structure. With permission from DeBrabander, DeMey, Geuens, Nuydens, Aerts, Willebrords and Moerman (1985).

Figure 5.12: Schematic representation of a microtubule associated protein (MAP dark lines) facilitating assembly of a microtubule (MT). The longitudinal binding retards dissociation of subunits and stabilizes the MT structure. With permission from DeBrabander, DeMey, Geuens, Nuydens, Aerts, Willebrords and Moerman (1985).

MTOC/centrioles are involved in orientation, shape, timing of division and growth. With MT and other cytoskeletal structures, MTOC/centrioles determine what cells do, when and how they do it, and what kind of cells they are! Are MTOC the command centers of the cytoskeleton? Chapter 3 described the significant position of centrioles and MT in evolution, and Chapter 8 will describe theories which explain centrioles' enigmatic capabilities. These include consideration (Bornens, 1979) that centrioles rotationally oscillate with a gyroscopic inertia which senses and establishes cell orientation to neighbor cells, tissue, environment, chemical gradient fields, gravity, and perhaps other factors. Centrioles seem to be a relatively immobile anchor around which other cytoskeletal elements move and are organized. Bornens suggests that centrioles communicate with actin filament networks by propagating conformational effects, and thus regulate cellular activities. Another centriole theory has been lodged by Northwestern University's Guenter Albrecht-Buehler (1977, 1985), who proposes that centrioles detect signals (such as infra-red, ultrasound, microwave) propagating linearly throughout the cytoplasm. Albrecht-Buehler has considered the design principles for a nanoscale directional signal detector and finds that centrioles are appropriate. Centrioles, or their future hybrids, may have interesting technological applications (Chapter 10).

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  • katariina
    How many centrioles are in the organizing center?
    10 months ago

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