Differential Binding Regulation of Microtubule-associated Proteins MAP1A, MAP1B, and MAP2 by Tubulin Polyglutamylation

The major neuronal post-translational modification of tubulin, polyglutamylation, can act as a molecular potentiometer to modulate microtubule-associated proteins (MAPs) binding as a function of the polyglutamyl chain length. The relative affinity of Tau, MAP2, and kinesin has been shown to be optim...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-04, Vol.276 (16), p.12839-12848
Main Authors: Bonnet, C, Boucher, D, Lazereg, S, Pedrotti, B, Islam, K, Denoulet, P, Larcher, J C
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Binding Sites
Binding, Competitive
Brain - metabolism
Brain Chemistry
Kinetics
Mice
Microtubule-Associated Proteins - isolation & purification
Microtubule-Associated Proteins - metabolism
Models, Chemical
Polyglutamic Acid - chemistry
Polyglutamic Acid - metabolism
Protein Subunits
Sodium Chloride - pharmacology
Tubulin - analogs & derivatives
Tubulin - chemistry
Tubulin - isolation & purification
Tubulin - metabolism
Urea - pharmacology
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Summary:The major neuronal post-translational modification of tubulin, polyglutamylation, can act as a molecular potentiometer to modulate microtubule-associated proteins (MAPs) binding as a function of the polyglutamyl chain length. The relative affinity of Tau, MAP2, and kinesin has been shown to be optimal for tubulin modified by ∼3 glutamyl units. Using blot overlay assays, we have tested the ability of polyglutamylation to modulate the interaction of two other structural MAPs, MAP1A and MAP1B, with tubulin. MAP1A and MAP2 display distinct behavior in terms of tubulin binding; they do not compete with each other, even when the polyglutamyl chains of tubulin are removed, indicating that they have distinct binding sites on tubulin. Binding of MAP1A and MAP1B to tubulin is also controlled by polyglutamylation and, although the modulation of MAP1B binding resembles that of MAP2, we found that polyglutamylation can exert a different mode of regulation toward MAP1A. Interestingly, although the affinity of the other MAPs tested so far decreases sharply for tubulins carrying long polyglutamyl chains, the affinity of MAP1A for these tubulins is maintained at a significant level. This differential regulation exerted by polyglutamylation toward different MAPs might facilitate their selective recruitment into distinct microtubule populations, hence modulating their functional properties.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M011380200