Regulation of microtubule dynamic instability
ABSTRACT Proper regulation of MT (microtubule) dynamics is essential for various vital processes, including the segregation of chromosomes, directional cell migration and differentiation. MT assembly and disassembly is modulated by a complex network of intracellular factors that co-operate or antagonize each other, are highly regulated in space and time and are thus attuned to the cell cycle and differentiation processes. While we only begin to appreciate how the concerted action of MT stabilizers and destabilizers shapes different MT patterns, a clear picture of how individual factors affect the MT structure is emerging. In this paper, we review the current knowledge about proteins that modulate MT dynamic instability.
Full-textDOI: · Available from: Anne Straube, Jun 10, 2015
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ABSTRACT: Author Summary Microtubules are cylindrical machines inside biological cells, and are crucial for many functions such as chromosome segregation, intra-cellular transport, and cell motility. They are made of 13 elastic filaments (protofilaments) that can be either in a straight or in a curved conformation depending on the chemical state of the constituent tubulin molecules. The interplay between these two conformations help microtubules to display a fascinating phenomenon known as “dynamic instability,” in which the microtubule steadily self-assembles and catastrophically disassembles in a seemingly random process. During the disassembly, the protofilaments are known to curve out forming ram’s horn-like structures. Scientists have been trying to understand how the laws of mechanics and statistical thermodynamics determine the complex behavior of microtubules. In this paper, we investigate how the chemical bonding between protofilaments, bending elasticity of protofilaments, and thermal forces determine the speed of the disassembly of the microtubule cylinder. We show that the current notion of a bending-elasticity dominated disassembly will lead to a paradox; resolving the paradox, we argue that the disassembly is a result of an intricate molecular orchestration in which the thermal and curvature energies of protofilaments compete with inter-protofilament bonding energy leading to curving out and depolymerization.PLoS Computational Biology 02/2015; 11(2):e1004099. DOI:10.1371/journal.pcbi.1004099 · 4.83 Impact Factor