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Microtubule nucleation
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Microtubule nucleation
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.
Microtubule nucleation occurs spontaneously in vitro, with solutions of purified tubulin giving rise to full-length polymers. The tubulin dimers that make up the polymers have an intrinsic capacity to self-aggregate and assemble into cylindrical tubes, provided there is an adequate supply of GTP. The kinetics barriers of such a process, however, mean that the rate at which microtubules spontaneously nucleate is relatively low.
In vivo, cells get around this kinetic barrier by using various proteins to aid microtubule nucleation. The primary pathway by which microtubule nucleation is assisted requires the action of a third type of tubulin, γ-tubulin, which is distinct from the α and β subunits that compose the microtubules themselves. The γ-tubulin combines with several other associated proteins to form a conical structure known as the γ-tubulin ring complex (γ-TuRC). This complex, with its 13-fold symmetry, acts as a scaffold or template for α/β tubulin dimers during the nucleation process—speeding up the assembly of the ring of 13 protofilaments that make up the growing microtubule. The γ-TuRC also acts as a cap of the (−) end while the microtubule continues growth from its (+) end. This cap provides both stability and protection to the microtubule (-) end from enzymes that could lead to its depolymerization, while also inhibiting (-) end growth.
The γ-TuRC is typically found as the core functional unit in a microtubule organizing center (MTOC), such as the centrosome in some animal cells or the spindle pole bodies in fungi and algae. The γ-TuRCs in the centrosome nucleate an array of microtubules in interphase, which extend their (+)-ends radially outwards into the cytoplasm towards the periphery of the cell. Among its other functions, this radial array is used by microtubule-based motor proteins to transport various cargoes, such as vesicles, to the plasma membrane.
The centrosome is the most common MTOC for multipotent cells in animals, with differentiated tissues utilising a wide variety of non-centrosomal MTOCs.
In animal cells undergoing mitosis, a similar radial array is generated from two MTOCs called the spindle poles, which produce the bipolar mitotic spindle. Some cells however, such as those of higher plants and oocytes, lack distinct MTOCs and microtubules are nucleated via a non-centrosomal pathway. Other cells, such as neurons, skeletal muscle cells, and epithelial cells, which do have MTOCs, possess arrays of microtubules not associated with a centrosome. These non-centrosomal microtubule arrays can take on various geometries—such as those leading to the long, slender shape of myotubes, the fine protrusions of an axon, or the strongly polarized domains of an epithelial cell.
In epithelial cells, CAMSAP3 acts as the non-centrosomal MTOC, and is localised to the apical membrane of the cell. Microtubules grow from this domain in parallel lines, giving the cell its rectangular shape.
The early cells of the pre-implantation mouse embryo utilise a unique non-centrosomal MTOC, in the form of an interphase microtubule bridge joining sister cells. This interphase bridge organises the microtubules of both cells, and uses CAMSAP3 to bind microtubule minus ends.
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Microtubule nucleation
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.
Microtubule nucleation occurs spontaneously in vitro, with solutions of purified tubulin giving rise to full-length polymers. The tubulin dimers that make up the polymers have an intrinsic capacity to self-aggregate and assemble into cylindrical tubes, provided there is an adequate supply of GTP. The kinetics barriers of such a process, however, mean that the rate at which microtubules spontaneously nucleate is relatively low.
In vivo, cells get around this kinetic barrier by using various proteins to aid microtubule nucleation. The primary pathway by which microtubule nucleation is assisted requires the action of a third type of tubulin, γ-tubulin, which is distinct from the α and β subunits that compose the microtubules themselves. The γ-tubulin combines with several other associated proteins to form a conical structure known as the γ-tubulin ring complex (γ-TuRC). This complex, with its 13-fold symmetry, acts as a scaffold or template for α/β tubulin dimers during the nucleation process—speeding up the assembly of the ring of 13 protofilaments that make up the growing microtubule. The γ-TuRC also acts as a cap of the (−) end while the microtubule continues growth from its (+) end. This cap provides both stability and protection to the microtubule (-) end from enzymes that could lead to its depolymerization, while also inhibiting (-) end growth.
The γ-TuRC is typically found as the core functional unit in a microtubule organizing center (MTOC), such as the centrosome in some animal cells or the spindle pole bodies in fungi and algae. The γ-TuRCs in the centrosome nucleate an array of microtubules in interphase, which extend their (+)-ends radially outwards into the cytoplasm towards the periphery of the cell. Among its other functions, this radial array is used by microtubule-based motor proteins to transport various cargoes, such as vesicles, to the plasma membrane.
The centrosome is the most common MTOC for multipotent cells in animals, with differentiated tissues utilising a wide variety of non-centrosomal MTOCs.
In animal cells undergoing mitosis, a similar radial array is generated from two MTOCs called the spindle poles, which produce the bipolar mitotic spindle. Some cells however, such as those of higher plants and oocytes, lack distinct MTOCs and microtubules are nucleated via a non-centrosomal pathway. Other cells, such as neurons, skeletal muscle cells, and epithelial cells, which do have MTOCs, possess arrays of microtubules not associated with a centrosome. These non-centrosomal microtubule arrays can take on various geometries—such as those leading to the long, slender shape of myotubes, the fine protrusions of an axon, or the strongly polarized domains of an epithelial cell.
In epithelial cells, CAMSAP3 acts as the non-centrosomal MTOC, and is localised to the apical membrane of the cell. Microtubules grow from this domain in parallel lines, giving the cell its rectangular shape.
The early cells of the pre-implantation mouse embryo utilise a unique non-centrosomal MTOC, in the form of an interphase microtubule bridge joining sister cells. This interphase bridge organises the microtubules of both cells, and uses CAMSAP3 to bind microtubule minus ends.