Microtubules are highly-dynamic structural and functional intracellular highways. The term cytoskeleton conjures up an image of rigid, immutable, and permanent structure. In reality, the cytoskeleton is a highly dynamic interconnected network composed of three different principal components: microtubules (polymerized tubulin dimers), microfilaments (polymerized actin), and intermediate filaments. Microtubules are the largest cytoskeletal components. They play a role in nearly every cellular process. They give structural stability and form to an otherwise amorphous cell. They are the principal components in an interconnected intracellular “highway” by which all manner cellular cargo may be shuttled via a bustling network of molecular motor proteins. During mitosis, microtubule contraction, focused at one of two mitotic spindles, provides the force necessary to divide chromosomes.
The ever changing nature of the cellular microenvironment necessitates adaptability, particularly during development. Microtubules and other cytoskeletal components facilitate this adaptability by virtue of their polymeric structure. The fundamental unit of the microtubule is a tubulin dimer, composed of one alpha tubulin-subunit, and one corresponding beta-tubulin subunit. These dimers polymerize to form a hollow, tubular structure approximately 24nm wide.
The natural state of unmodified tubulin is one of constant flux, with a nearly equal rate of polymerization and depolymerization. Several common GTPase families like Rac and Rho promote microtubule assembly indirectly by facilitating GDP/GTP exchange on regulatory members that effect assembly and disassembly of tubulin dimers. Other microtubule stabilizers take a more direct approach. Microtubule associated proteins like MAP1, MAP2, MAP4, or MAPtau bind polymerized microtubules stabilize the polymerized form, promoting assembly and microtubule growth. Most MAPs are activated by phosphorylation, and MAPK (map kinase) phosphorylation cascades add an additional layer of control to the process of microtubule assembly.
Conversely, cells have several different ways to regulate microtubule disassembly. Direct methods for promoting disassembly include components like Stathmin, which binds alpha/beta-tubulin dimers and prevents them from polymerizing. Microtubule severing enzymes like Katanin are able to break microtubules in the middle of their structure, while Kinesin I family members like KIF2 walk along microtubules and promote “fraying” and depolymerization.
Microtubule-associated proteins
CLASP1 (Cytoplasmic Linker Associated Protein 1):
CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170\; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008].
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This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as...
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Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent...
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Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent...
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This gene encodes a member of the tubulin superfamily. This protein localizes to the centriolar sub-distal appendages that are associated with the older of the two centrioles after centrosome duplication. This protein plays a central role in organization of the microtubules during centriole duplication. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Jan 2009].
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CLIP1 (CAP-GLY Domain Containing Linker Protein 1):
The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011].
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The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to...
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CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170\; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008].
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The protein encoded by this gene is a member of kinesin-like protein family. Proteins of this family are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein is important for anaphase chromosome segregation and may be required to coordinate the onset of sister centromere separation. [provided by RefSeq, Jul 2008].
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The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. Mouse Skd1 (suppressor of K+...
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