Transglutaminase and Polyamination of Tubulin: Posttranslational Modification for Stabilizing Axonal Microtubules

• DOI: 10.1016/j.neuron.2013.01.036
• Publication Date: 2013-04-16T17:15:57Z
• Authors: Yuyu Song; Laura L. Kirkpatrick; Alexander B. Schi...; Donald L. Helseth; Nicolas Chabot; Jeffrey W. Keillor; Gail V.W. Johnson; Scott T. Brady
• Keywords: Male; Mice, Knockout; Models, Molecular; 0303 health sciences; Magnetic Resonance Spectroscopy; Neuroscience(all); Brain; Cell Fractionation; Microtubules; Models, Biological; Axons; Mice, Inbred C57BL; Mice; Neuroblastoma; 03 medical and health sciences; GTP-Binding Proteins; Neurites; Polyamines; Animals; Protein Glutamine gamma Glutamyltransferase 2; Enzyme Inhibitors; Chromatography, High Pressure Liquid; Cell Line, Transformed

Neuronal microtubules support intracellular transport, facilitate axon growth, and form a basis for neuronal morphology. While microtubules in nonneuronal cells are depolymerized by cold, Ca(2+), or antimitotic drugs, neuronal microtubules are unusually stable. Such stability is important for normal axon growth and maintenance, while hyperstability may compromise neuronal function in aging and degeneration. Though mechanisms for stability are unclear, studies suggest that stable microtubules contain biochemically distinct tubulins that are more basic than conventional tubulins. Transglutaminase-catalyzed posttranslational incorporation of polyamines is one of the few modifications of intracellular proteins that add positive charges. Here we show that neuronal tubulin can be polyaminated by transglutaminase. Endogenous brain transglutaminase-catalyzed polyaminated tubulins have the biochemical characteristics of neuronal stable microtubules. Inhibiting polyamine synthesis or transglutaminase activity significantly decreases microtubule stability in vitro and in vivo. Together, these findings suggest that transglutaminase-catalyzed polyamination of tubulins stabilizes microtubules essential for unique neuronal structures and functions.