Principles of Microtubule Organization: Insight from the Study of Neurons
A multitude of protein activities contribute to the organization of cell type and cell cycle-specific microtubule arrays. One key factor is the γ-tubulin ring complex (γTuRC), a microtubule nucleator that determines where and when new microtubules are gen
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Principles of Microtubule Organization: Insight from the Study of Neurons Carlos Sa´nchez-Huertas, Francisco Freixo, and Jens Lu¨ders
Abstract
A multitude of protein activities contribute to the organization of cell type and cell cycle-specific microtubule arrays. One key factor is the γ-tubulin ring complex (γTuRC), a microtubule nucleator that determines where and when new microtubules are generated. Other proteins interact with newly formed or existing microtubules to promote microtubule stabilization, destabilization, severing, bundling, or transport. Together these activities allow arrangement of microtubules into arrays with specific distribution, polarity, and dynamic properties. Importantly, microtubule arrays are not static and can undergo extensive remodeling. During neural development, for example, self-renewing and neurogenic divisions of neural progenitors require specific spindle positioning, which is determined by centrosome-based microtubule organization. In newly born neurons, the centrosomal microtubule array mediates the migration process. However, during neuron maturation the centrosome-centered microtubule network is converted into non-centrosomal, highly bundled arrays, which are crucial for long-range transport within the extensive dendritic and axonal compartments. Accordingly, neuronal development, homeostasis and function are particularly sensitive to genetic and other insults of the microtubule cytoskeleton. In this chapter we will highlight, using neurons as an example, different microtubule-organizing activities, in particular microtubule nucleation and its spatiotemporal regulation, and discuss how defects in the microtubule network are implicated in neurodevelopmental disorders and neurodegenerative diseases.
C. Sa´nchez-Huertas • F. Freixo • J. Lu¨ders (*) Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, Barcelona 08028, Spain e-mail: [email protected] # Springer-Verlag Wien 2016 J. Lu¨ders (ed.), The Microtubule Cytoskeleton, DOI 10.1007/978-3-7091-1903-7_4
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4.1
Cellular Tools for Organizing Microtubules
4.1.1
Microtubule Nucleation
A key mechanism underlying assembly, maintenance, and remodeling of ordered microtubule arrays is microtubule nucleation. Spatiotemporal regulation of this process allows cells to control when, where, and in what orientation new microtubules are formed (Luders and Stearns 2007; Teixido-Travesa et al. 2012; Yau et al. 2014). Above a critical tubulin concentration, polymerization from purified tubulin occurs spontaneously in vitro. In cells, however, the tubulin concentration is too low to allow spontaneous polymerization and formation of microtubules requires a nucleator. In animal cells microtubules are nucleated by the multi-subunit γ-tubulin ring complex (γTuRC). γTuRC is composed of γ-tubulin, a member of the tubulin superfamily that is not incorporated into the microtubule polymer, and additional subunits known as gamma
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