Posttranslational Modifications of Tubulin and Cilia

Abstract

Tubulin undergoes several highly conserved posttranslational modifications (PTMs) including acetylation, detyrosination, glutamylation, and glycylation. These PTMs accumulate on a subset of microtubules that are long-lived, including those in the basal bodies and axonemes. Tubulin PTMs are distributed nonuniformly. In the outer doublet microtubules of the axoneme, the B-tubules are highly enriched in the detyrosinated, polyglutamylated, and polyglycylated tubulin, whereas the A-tubules contain mostly unmodified tubulin. The nonuniform patterns of tubulin PTMs may functionalize microtubules in a position-dependent manner. Recent studies indicate that tubulin PTMs contribute to the assembly, disassembly, maintenance, and motility of cilia. In particular, tubulin glutamylation has emerged as a key PTM that affects ciliary motility through regulation of axonemal dynein arms and controls the stability and length of the axoneme.

Figure 1.

Conserved and widely studied types of tubulin posttranslational modifications (PTMs) and the responsible enzymes that act in cilia. CTT, Carboxy-terminal tail; TTL(L), tubulin tyrosine ligase(-like); CCP, cytosolic carboxypeptidase.

Figure 2.

The nonuniform patterns of tubulin PTMs in cilia. (A-C) A Tetrahymena cell labeled with antibodies that recognize either polyglutamate (poly-E, green) (Shang et al. 2002) or polyglycine side chains (AXO49) (Bré et al. 1998). Note that the shorter assembling cilia (arrows) have a higher signal of polyglutamylation and a lower signal of polyglycylation as compared to the longer mature cilia on the same cell. These data suggest that during their assembly, cilia undergo remodeling of tubulin PTMs. (Figure adapted from Sharma et al. 2007; originally published in Journal of Cell Biology.) (D) A superresolution structured illumination microscopy (SR-SIM) image of the posterior end of a Tetrahymena cell, with cilia labeled with poly-G (green) (Duan and Gorovsky 2002) and anti-α-tubulin primary sequence antibodies 12G10 (red) (Jerka-Dziadosz et al. 1995). Note an absence of a signal of poly-G near the tips of cilia (distal segment) where the B-tubules are absent. (E) A postembedding immunogold image of cross sections of Tetrahymena cilia labeled with antipolyglycine AXO49 antibodies. Note the absence of a signal near the central microtubules. (From Wloga et al. 2009; adapted, with permission.) (F) An isolated doublet microtubule of Chlamydomonas labeled by poly-E antibodies with 10 nm colloidal gold and negatively stained with uranyl acetate. The A-tubule side can be identified by the presence of dynein arms (top), whereas the B-tubule has a smoother surface (bottom). Note that the gold particles are enriched along the B-tubule. (From Kubo et al. 2010; reprinted, with permission, from Elsevier © 2010.)