Biology Reference
In-Depth Information
Box 16.1 CHARACTERISTICS OF TUBULIN PTMs
Acetylation
The best-analyzed acetylation site of a-tubulin is lysine residue number 40 (
LeDizet & Piperno,
1987
). Recently, additional acetylation sites have been found in a proteomic study (
Choudhary
et al., 2009
) but not been confirmed otherwise. Lysine-40 acetylation is catalyzed by the acetyl
transferases Atat-1 (Mec-17) and Atat-2 (
Akella et al., 2010; Shida et al., 2010
); however,
other acetyl transferases, such as Elp3 (
Creppe et al., 2009
), are also involved in tubulin
acetylation. Tubulin acetylation is reversed by the deacetylases HDAC6 (
Hubbert et al., 2002
)
and SIRT2 (
North, Marshall, Borra, Denu, & Verdin, 2003
). Because of its localization at the
inside of MTs (
Soppina, Herbstman, Skiniotis, & Verhey, 2012
), lysine-40 acetylation does not
directly regulate motor traffic on MTs (
Walter, Beranek, Fischermeier, & Diez, 2012
), but plays
an important role in MT assembly (
Cueva, Hsin, Huang, & Goodman, 2012; Topalidou et al.,
2012
).
Detyrosination/Tyrosination
Detyrosination removes the terminal, gene-encoded tyrosine froma-tubulin (
Hallak, Rodriguez,
Barra, & Caputto, 1977; Valenzuela et al., 1981
). This modification is reversible (
Arce,
Rodriguez, Barra, & Caputo, 1975; Raybin & Flavin, 1975
) and returosination is catalyzed by a
well-characterized enzyme, tubulin tyrosine ligase (TTL;
Ersfeld et al., 1993
). Strikingly, the
enzymes catalyzing detyrosination have remained unknown despite great efforts to identify
them. Detyrosinated tubulin is sometimes referred to as Glu-tubulin, which often leads to
confusion with polyglutamylated tubulin.
Following detyrosination, the C-terminal tail of a-tubulin can be further shortened by the
removal of the penultimate glutamate residue generating D2-tubulin (
Paturle-Lafanechere
et al., 1991
). This deglutamylation reaction is catalyzed by enzymes from the cytosolic
carboxypeptidase (CCP) family, which are also involved in the removal of posttranslationally
added polyglutamylation (see below;
Rogowski et al., 2010
). Further proteolysis of the
C-terminal tubulin tail can occur to generate D3-tubulin (
Berezniuk et al., 2012
). D2-Tubulin
is an irreversibly modified form of a-tubulin, as it cannot be retyrosinated (
Paturle-Lafanechere
et al., 1991; Prota et al., 2013
). Detyrosination (and its derivate D2-tubulin) is accumulated on
rather stable MT species (
Gundersen, Kalnoski, & Bulinski, 1984; Paturle-Lafanechere et al.,
1994; Schulze, Asai, Bulinski, & Kirschner, 1987
). Detyrosination enhances kinesin-1-driven
transport in neurons (
Konishi & Setou, 2009
), but inhibits the MT-plus-end tracking of CAP-Gly
domain proteins (
Bieling et al., 2008; Peris et al., 2006
) and the MCAK-driven
depolymerization of MTs (
Peris et al., 2009
).
Polyglutamylation
Polyglutamylation consists of the addition of glutamate side chains of different lengths on
glutamate residues within the C-terminal tails of a- and b-tubulins (
Edd´ et al., 1990; R¨ diger
et al., 1992
). Polyglutamylation is catalyzed by enzymes of the tubulin tyrosine ligase-like
(TTLL) family (
Janke et al., 2005
). Various members of this family have distinct reaction
specificities (initiation vs. elongation of the side chains; a- vs. b-tubulin), which result in the
generation of different polyglutamylation patterns on MTs in cells (
van Dijk et al., 2007
).
Polyglutamylation is removed by deglutamylases from the CCP family that, equivalent to the
TTLLs, specifically either shorten long side chains, or remove the short chains including the
branching point (
Rogowski et al., 2010
).
Polyglutamylation is expected to regulate multiple interactions between MTs and their
associated proteins, such as MAPs and molecular motors. The first regulatory events have been
demonstrated with the MT-severing enzyme spastin (
Lacroix et al., 2010
), and several
publications have shown an important role in ciliary beating (e.g.,
Lee et al., 2012; Suryavanshi
et al., 2010
).
