Microtubule-Associated Protein 1B Interaction with Tubulin Tyrosine Ligase Contributes to the Control of Microtubule Tyrosination

Abstract

Microtubule-associated protein 1B (MAP1B) is the first microtubule-associated protein to be expressed during nervous system development. MAP1B belongs to a large family of proteins that contribute to the stabilization and/or enhancement of microtubule polymerization. These functions are related to the control of the dynamic properties of microtubules. The C-terminal domain of the neuronal α-tubulin isotype is characterized by the presence of an acidic polypeptide, with the last amino acid being tyrosine. This tyrosine residue may be enzymatically removed from the protein by an unknown carboxypeptidase activity. Subsequently, the tyrosine residue is again incorporated into this tubulinby another enzyme, tubulin tyrosine ligase, to yield tyrosinated tubulin. Because neurons lacking MAP1B have a reduced proportion of tyrosinated microtubules, we analyzed the possible interaction between MAP1B and tubulin tyrosine ligase. Our results show that these proteins indeed interact and that the interaction is not affected by MAP1B phosphorylation. Additionally, neurons lacking MAP1B, when exposed to drugs that reversibly depolymerize microtubules, do not fully recover tyrosinated microtubules upon drug removal. These results suggest that MAP1B regulates tyrosination of α-tubulin in neuronal microtubules. This regulation may be important for general processes involved in nervous system development such as axonal guidance and neuronal migration.

Microtubule-associated Protein 1B (MAP1B) Is Required for Dendritic Spine Development and Synaptic Maturation

“…Indeed, MTs were assumed to be absent from dendritic spines until the transient entry of dynamic MTs into dendritic spines was recently described (32)(33)(34). MAP1B is an MT-associated protein that is implicated in the maintenance of dynamic MT populations (66,67), and it interacts directly with actin (37,38). Thus, it is reasonable to hypothesize that MAP1B can enter into dendritic spines in association with either dynamic MTs or actin microfilaments.…”

“…Interestingly, MAP1B increases the amount of tyrosinated (i.e. more dynamic) MTs through a mechanism involving the interaction of MAP1B with the enzyme tubulin tyrosine ligase (67). It has been proposed that the transient entry of MTs into dendritic spines serves as a signal to locally reorganize the actin cytoskeleton and regulate spine size (33,34).…”

Role of the RNA-Binding Protein IMP-2 in Muscle Cell Motility

“…Posttranslational modifications of tubulin in cells are regulated by a cycle of tyrosination/detyrosination, performed by tubulin tyrosine ligase (TTL) and tubulin carboxypeptidase (4). In addition, several proteins have been reported to directly bind to and stabilize the MTs via specific accumulation of detyrosinated tubulin (37,40). Another mechanism of regulation of MT remodeling occurs at the level of focal adhesions (FAs), cytoplasmic and membrane structures which are indispensable for cellular adhesion, motility, and cytoskeleton integrity (11,30).…”

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

“…Some of them, like tau or MAP2, induce MT bundling, whereas others like MAP4 do not have bundling activity (Burgin et al 1994;Kanai et al 1989Nguyen et al 1997;Olson et al 1995). In addition, MAP1B has been shown to control MT dynamic, while MAP4 alters MT surface properties and affects motor protein activity Samora et al 2011;Semenova et al 2014;Tokuraku et al 2007;Tortosa et al 2013;Utreras et al 2008). Interestingly, many of these MAPs not only bind MTs but also interact with actin and participate in numerous signal pathways.…”

“…MAP1B, compared with other MAPs, is a weak MT stabilizer (Takemura et al 1992). Recent studies suggest that MAP1B preferably associates to dynamic, tyrosinated MTs Tymanskyj et al 2012;Utreras et al 2008). MAP1B also interacts with other MT-interacting proteins, including tubulin-tyrosine ligase and EB1/EB3, dynein regulators like LIS1, scaffolding proteins such as dystonin-α2, and motor protein KIF21A (Cheng et al 2014;Villarroel-Campos and Gonzalez-Billault 2014).…”