Tubulin posttranslational modifications as regulators of microtubule-based functions in cells

摘要

Microtubules (MT) form a dynamic intracellular networkthat plays essential roles in cellular function and development.They are also the structural components of cilia andflagella. MTs maintain cilia structure and dynamics by thespecific interaction of a large set of MT-associated proteins,including molecular motors and MAPs. How theinteractions between MTs and their multiple associatedproteins are spatio-temporally is not known. An increasingbody of evidence supports that tubulin posttranslationalmodifications(PTMs) have a key role in regulating therecruitment of protein complexes in the MT because theyallow for a rapid, reversible and locally restricted generationof MT diversity. In particular, two PTMs, glutamylationand glycylation are strongly enriched in the cilium.Glycylation is restricted to axonemal MTs, suggesting ahighly specialised function, whereas glutamylation is alsopresent in centrioles and basal bodies. Our hypothesis isthat differentially glutamylated/glycylated MTs can distinguishMT subpopulations in the cilium allowing for therecruitment of specific proteins. Here we address the roleof glutamylation and glycylation in cilia, by modulatingthe extent of each modification using the ependymal cellsystem as a model. We study the role of both modificationsin cilia physiology, including cilia assembly, maintenanceand beating. Our data demonstrate that glycylationis essential for cilia maintenance, whereas glutamylation isrequired for cilia beating. Taken together, tubulin PTMsare likely to play an important role for cilia and could possiblybeen linked to human disorders known to be associatedwith defects in MT-based traffic, such as ciliarydysfunctions (ciliopathies).