A targeted multienzyme mechanism for selective microtubule polyglutamylation.
Polyglutamylases are enzymes that form polyglutamate side chains of variable lengths on proteins. Polyglutamylation of tubulin is believed to regulate interactions of microtubules (MTs) with MT-associated proteins and molecular motors. Subpopulations of MTs are differentially polyglutamylated, yet only one modifying enzyme has been discovered in mammals. In an attempt to better understand the heterogeneous appearance of tubulin polyglutamylation, we searched for additional enzymes and report here the identification of six mammalian polyglutamylases. Each of them has a characteristic mode of catalysis and generates distinct patterns of modification on MTs, which can be further diversified by cooperation of multiple enzymes. Polyglutamylases are restricted to confined tissues and subtypes of MTs by differential expression and localization. In conclusion, we propose a multienzyme mechanism of polyglutamylation that can explain how the diversity of polyglutamylation on selected types of MTs is controlled at the molecular level.
van Dijk
Juliette
J
CRBM, CNRS, 34293 Montpellier, France.
Rogowski
Krzysztof
K
Miro
Julie
J
Lacroix
Benjamin
B
Eddé
Bernard
B
Janke
Carsten
C
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014404:Tubulin / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D011099:Polyglutamic Acid; D010453:Peptide Synthases; C022414:polyglutamyl synthetase; C112698:tubulin polyglutamylase