title: Transglutaminase and polyamination of tubulin: posttranslational modification for stabilizing axonal microtubules.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Song
authors.forename: Laura L
authors.initials: LL
authors.lastname: Kirkpatrick
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Schilling
authors.forename: Donald L
authors.initials: DL
authors.lastname: Helseth
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chabot
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Keillor
authors.forename: Gail V W
authors.initials: GV
authors.lastname: Johnson
authors.forename: Scott T
authors.initials: ST
authors.lastname: Brady
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002458:Cell Fractionation; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000172:deficiency*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology; D011073:Polyamines / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011503:Transglutaminases / Q000172:deficiency*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011073:Polyamines; D014404:Tubulin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins