The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation.
Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by α-tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name αTAT1, with a highly specific α-tubulin K40 acetyltransferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of αTAT1 is necessary and sufficient for α-tubulin K40 acetylation. Remarkably, αTAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of αTAT1, and its paralog αTAT-2 are required for α-tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, αTAT-2, and the sole C. elegans K40α-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that αTAT1 is the major and possibly the sole α-tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5345, USA.
Toshinobu
T
Shida
Juan G
JG
Cueva
Zhenjie
Z
Xu
Miriam B
MB
Goodman
Maxence V
MV
Nachury
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology; D013379:Substrate Specificity; D014110:Touch / Q000502:physiology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D014404:Tubulin; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase