Abstract
Distinctly organized microtubule networks contribute to the function of differentiated cell types such as neurons, epithelial cells, skeletal myotubes, and cardiomyocytes. In striated (i.e., skeletal and cardiac) muscle cells, the nuclear envelope acts as the dominant microtubule-organizing center (MTOC) and the function of the centrosome—the canonical MTOC of mammalian cells—is attenuated, a common feature of differentiated cell types. We summarize the mechanisms known to underlie MTOC formation at the nuclear envelope, discuss the significance of the nuclear envelope MTOC for muscle function and cell cycle progression, and outline potential mechanisms of centrosome attenuation.
Highlights
Non-Centrosomal Microtubule-Organizing Centers—A Hallmark of DifferentiationMicrotubules are an integral part of the cytoskeleton, playing important roles in cellular processes such as intracellular trafficking, cell division, and maintenance of cellular architecture including shape, polarity, and organelle positioning
We focus on striated muscle (1) to summarize mechanisms of non-centrosomal MTOCs (ncMTOCs) formation, (2) to illuminate diverse functional aspects of ncMTOCs, and (3) to discuss the interplay of ncMTOC formation and cell cycle
While the centrosome is pivotal for animal cells to ensure fidelity and proper orientation of cell division, several microtubule-mediated processes are organized by centrosome-independent pathways
Summary
Microtubules are an integral part of the cytoskeleton, playing important roles in cellular processes such as intracellular trafficking, cell division, and maintenance of cellular architecture including shape, polarity, and organelle positioning. In the course of re-organization, the centrosomal MTOC function is attenuated and microtubules are mainly organized from other subcellular sites, termed non-centrosomal MTOCs (ncMTOCs) [2]. This shift from a centrosomal MTOC to ncMTOCs occurs to varying degrees in different cell types. Neurons and striated (i.e., skeletal and cardiac) muscle cells only retain vestigial MTOC activity at centrosomes while dominant MTOC function is exhibited by non-centrosomal sites in these cells [4,5,6]. Transition from centrosomal MTOCs to ncMTOCs occurs mainly in cells that—under physiological conditions—permanently exit the cell cycle during differentiation. We focus on striated muscle (1) to summarize mechanisms of ncMTOC formation, (2) to illuminate diverse functional aspects of ncMTOCs, and (3) to discuss the interplay of ncMTOC formation and cell cycle
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