Tubulin polyglutamylation stimulates spastin-mediated microtubule severing.
Posttranslational glutamylation of tubulin is present on selected subsets of microtubules in cells. Although the modification is expected to contribute to the spatial and temporal organization of the cytoskeleton, hardly anything is known about its functional relevance. Here we demonstrate that glutamylation, and in particular the generation of long glutamate side chains, promotes the severing of microtubules. In human cells, the generation of long side chains induces spastin-dependent microtubule disassembly and, consistently, only microtubules modified by long glutamate side chains are efficiently severed by spastin in vitro. Our study reveals a novel control mechanism for microtubule mass and stability, which is of fundamental importance to cellular physiology and might have implications for diseases related to microtubule severing.
Centre de Recherche de Biochimie Macromoléculaire, Université Montpellier 2 and 1, Centre National de la Recherche Scientifique UMR 5237, Montpellier, France.
Benjamin
B
Lacroix
Juliette
J
van Dijk
Nicholas D
ND
Gold
Julien
J
Guizetti
Gudrun
G
Aldrian-Herrada
Krzysztof
K
Rogowski
Daniel W
DW
Gerlich
Carsten
C
Janke
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D000074201:Katanin; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000074181:Spastin; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D007527:Isoenzymes; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D018698:Glutamic Acid; D000251:Adenosine Triphosphatases; D000074181:Spastin; D000074201:Katanin; C400283:SPAST protein, human; D010453:Peptide Synthases; C112698:tubulin polyglutamylase