Unique Post-Translational Modifications in Specialized Microtubule Architecture

Abstract

ABSTACT.Microtubules (MTs) play specialized roles in a wide variety of cellular events, e.g. molecular transport, cell motility, and cell division. Specialized MT architectures, such as bundles, axonemes, and centrioles, underlie the function. The specialized function and highly organized structure depend on interactions with MT-binding proteins. MT-associated proteins (e.g. MAP1, MAP2, and tau), molecular motors (kinesin and dynein), plus-end tracking proteins (e.g. CLIP-170), and MT-severing proteins (e.g. katanin) interact with MTs. How can the MT-binding proteins know temporospatial information to associate with MTs and to properly play their roles? Post-translational modifications (PTMs) including detyrosination, polyglutamylation, and polyglycylation can provide molecular landmarks for the proteins. Recent efforts to identify modificationregulating enzymes (TTL, carboxypeptidase, polyglutamylase, polyglycylase) and to generate genetically manipulated animals enable us to understand the roles of the modifications. In this review, we present recent advances in understanding regulation of MT function, structure, and stability by PTMs.

A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT-based processes in mammalian cells

“…determine the subset of MT with which each different complex could interact). Conceivably, the distribution of specific tubulin isoforms or post-translational modifications to distinct MT subsets can create discrete MT subpopulations with unique functionality [51,52] and severing enzyme affinities and thus also contribute to substrate specialization. Given the extensive sequence similarity between the KATNAL2 isoforms and likely low abundance of specific complexes, it would be technically challenging to address such scenarios directly.…”

Immunohistochemical Overexpression of MAP-2 in the Cerebral Cortex of Rabies-Infected Mice

“…The phosphorylation of MAP-2 leads to the polymerization and increased rigidity of microtubules (Sánchez et al, 2000;Ikegami & Setou, 2010). It is interesting to note that the mRNAs of MAP-2 and CAMKII have in common that they are located in greater proportion in the neuronal dendrites of adult brains (Kuhl & Skehel, 1998), and CAMKII can phosphorylate MAP-2, increasing its ability to bind microtubules (Conde & Cáceres).…”

Cytosolic Carboxypeptidase 1 Is Involved in Processing α- and β-Tubulin

“…Most forms of mammalian ␣-tubulin are initially produced with a C-terminal Tyr residue encoded in the gene; this form is named "Tyr-tubulin." The Tyr is enzymatically removed to produce deTyr-tubulin (18,21). The deTyr-tubulin can be converted back to Tyr-tubulin through the addition of Tyr by the enzyme tubulin tyrosine ligase (TTL) (22).…”

“…The deTyr-tubulin can be converted back to Tyr-tubulin through the addition of Tyr by the enzyme tubulin tyrosine ligase (TTL) (22). Alternatively, the deTyr-tubulin can be converted to delta2-tubulin by the removal of C-terminal Glu (18,23). Another post-translational modification of ␣-tubulin as well as ␤-tubulin involves the addition and removal of polyglutamyl (polyE) side chains (18,24).…”

“…Alternatively, the deTyr-tubulin can be converted to delta2-tubulin by the removal of C-terminal Glu (18,23). Another post-translational modification of ␣-tubulin as well as ␤-tubulin involves the addition and removal of polyglutamyl (polyE) side chains (18,24). Tubulin glutamylation is performed by some members of the family of TTL-like proteins (25)(26)(27).…”