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Man toTrypanosome: The tubulin tyrosination/detyrosination cycle revisited

2000; Wiley; Volume: 45; Issue: 3 Linguagem: Inglês

10.1002/(sici)1097-0169(200003)45

1097-0169

Haitham T. Idriss,

Lysosomal Storage Disorders Research

Microtubules are a major component of the cytoskeleton and are vital for the function and viability of eukaryotic cells.They participate in processes such as maintaining cell shape, chromosome segregation during cell division, intracellular transport, and cell secretion.Microtubules are polymers of the protomer tubulin, a globular protein consisting of two subunits (␣-and ␤-tubulin) of approximately 55 kDa each.They are sensitive to low temperature, calcium, and a variety of drugs (many used as anti-cancer drugs) that induce depolymerisation or arrest polymer formation.Microtubules are stabilised by a number of accessory proteins termed "Microtubule Associated Proteins" (MAPs) such as MAP-2 and Tau.In cells, microtubules are usually nucleated by specialised structures termed "microtubule organising centers" (MTOCs), which include centrosomes and basal bodies [Bershadsky and Vasiliev, 1988;Brinkley, 1985;Dustin, 1978;Rieder and Salmon, 1998;Tucker, 1992].Two models describe the behaviour of assembled microtubules.The treadmilling model proposes net polymerisation of microtubules at one end and net depolymerisation at the other, leading to subunit flux at steady state, maintaining both constant polymer mass and mean length [Margolis and Wilson, 1981].Alternatively, "dynamic instability" suggests the coexistence of two interchangeable microtubule populations, a slowly growing population and a rapidly shrinking one [Mitchison and Kirschner, 1984], resulting in an absence of a true steady state for individual microtubules, but rather stochastic length changes.Both models have been proposed to occur in vivo [Margolis and Wilson, 1998;Schulze and Kirschner, 1988] and to be concomitantly in operation [Walker et al., 1988].Understanding processes that govern the assembly, stability, dynamics, and interactions of microtubules should enhance our understanding of cell cycling and regulation. TUBULIN, THE BUILDING BLOCK OF MICROTUBULESThree distinct forms of tubulin have been identified thus far, which are termed ␣, ␤ and ␥; and are each highly conserved.The ␣and ␤-tubulin subunits show † The term used by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB,see http://www.chem.qmw.ac.uk/iubmb/nomenclature/) is tyrosination.It uses this in listing EC 6.3.2.25, tubulin-tyrosine ligase (see http:// www.chem.qmw.ac.uk/iubmb/enzyme/).Bulinski and Gundersen [1986] give the arguments for preferring this term, based on the recommendations on naming derivatives of amino acids (see entries 3AA-1, 3AA-9.3, and 3AA-10.3 in http://www.chem.qmw.ac.uk/ iupac/AminoAcid /).Briefly, Tyrosylation would be misleading, since "tyrosyl" is the name of the acyl group, e.g., an N-terminal tyrosine residue, and acylation would suggest adding at the N-terminus.Tyrosinylation has almost the same implications, as it looks so like "tyrosyl."Tyrosinolation would also be misleading, as "tyrosinol" is defined as the alcohol in formed by reducing the -COOH of tyrosine to -CH 2 OH.Tyrosine ligation is also acceptable since TTL essentially carries out a ligation reaction.