Generation of noncentrosomal microtubule arrays

Abstract

In most proliferating and migrating animal cells, the centrosome is the main site for microtubule (MT) nucleation and anchoring, leading to the formation of radial MT arrays in which MT minus ends are anchored at the centrosomes and plus ends extend to the cell periphery. By contrast, in most differentiated animal cell types, including muscle, epithelial and neuronal cells, as well as most fungi and vascular plant cells, MTs are arranged in noncentrosomal arrays that are non-radial. Recent studies suggest that these noncentrosomal MT arrays are generated by a three step process. The initial step involves formation of noncentrosomal MTs by distinct mechanisms depending on cell type: release from the centrosome, catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The second step involves transport by MT motor proteins or treadmilling to sites of assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type-specific arrays by bundling and/or capture at cortical sites, during which MTs acquire stability. Despite their relative stability, the final noncentrosomal MT arrays may still exhibit dynamic properties and in many cases can be remodeled.

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

“…However, mitotic spindles can form in the absence of centrosomes through actions of motor proteins and structural elements (Theirkauf and Hawley, 1992;Bartolini and Gundersen, 2006;Walczak et al, 1998;Compton, 1998;McKim and Hawley, 1995;Matthies et al, 1996;Heald et al, 1997). It is commonly believed that centrosome functions have not been fully elucidated.…”

“…Whereas, anastral spindles formation relies on selfassembly. Anastral spindle assembly is prevalent in higher plants, meiotic cells and in some other cell types (Theirkauf and Hawley, 1992;Bartolini and Gundersen, 2006). In the process of spindle self-assembly, chromatin promotes microtubule polymerisation and actions of motor proteins aid sorting and organisation of microtubules into a bipolar spindle array (McKim, and Hawley, 1995;Heald et al, 1997;Theurkauf and Hawley, 1992;Matthies et al, 1996;Khodjakov and Rieder, 2001).…”

Noncentrosomal microtubules in C. elegans epithelia

“…A major task of centrosomal MTs is to assemble the mitotic spindle and to ensure proper chromosome segregation upon cell division (Desai and Mitchison, 1997). Later in embryonic development, when epithelial cells differentiate and polarize, centrosomes are inactivated and MTs become organized from noncentrosomal sites (Bartolini and Gundersen, 2006;Keating and Borisy, 1999;Mogensen, 1999). In most cases, MTs in epithelia are organized in parallel arrays, running along the apical-basal axis of the cell (Bartolini and Gundersen, 2006;Musch, 2004).…”

“…Later in embryonic development, when epithelial cells differentiate and polarize, centrosomes are inactivated and MTs become organized from noncentrosomal sites (Bartolini and Gundersen, 2006;Keating and Borisy, 1999;Mogensen, 1999). In most cases, MTs in epithelia are organized in parallel arrays, running along the apical-basal axis of the cell (Bartolini and Gundersen, 2006;Musch, 2004). Although these two types of MTs differ in their global organization and function, they share three properties: (i) their nucleation requires the g-tubulin ring complex (known as g-TuRC) (Bartolini and Gundersen, 2006;Keating and Borisy, 1999;Mogensen et al, 2000;Petry and Vale, 2015); (ii) once nucleated, their minus-ends require protein complexes to cap and anchor them (Akhmanova and Hoogenraad, 2015); and (iii) they harbor dynamic properties, in part conferred by plus-end targeting proteins (Akhmanova and Steinmetz, 2015).…”

“…In most cases, MTs in epithelia are organized in parallel arrays, running along the apical-basal axis of the cell (Bartolini and Gundersen, 2006;Musch, 2004). Although these two types of MTs differ in their global organization and function, they share three properties: (i) their nucleation requires the g-tubulin ring complex (known as g-TuRC) (Bartolini and Gundersen, 2006;Keating and Borisy, 1999;Mogensen et al, 2000;Petry and Vale, 2015); (ii) once nucleated, their minus-ends require protein complexes to cap and anchor them (Akhmanova and Hoogenraad, 2015); and (iii) they harbor dynamic properties, in part conferred by plus-end targeting proteins (Akhmanova and Steinmetz, 2015). Of note, although RNAi-mediated depletion of g-tubulin in C. elegans embryos reduces by 60% the level of MTs compared to wild-type embryos (Srayko et al 2005, O'Toole et al 2012, no bona fide g-tubulinindependent-microtubule nucleation pathway has thus far been reported (Petry and Vale, 2015).…”