The mechanism and significance of microtubule acetylation
Akella, Jyothi Shilpa
MetadataShow full item record
Lysine acetylation of αlpha tubulin is a conserved post-translational modification that is present on microtubules in many structures including cilia, neuronal projections and the spindle apparatus. The enzyme that acetylates microtubules and the significance of microtubule acetylation has been unknown. mec-17 is a gene highly expressed in the touch receptor neurons of C. elegans and was identified in a screen for genes required for touch sensation. mec-17 encodes a highly conserved protein with distant homology to the GCN5 family of histone acetyltransferases. MEC-17 is expressed in all organisms with acetylated microtubules. Using complementary genetic approaches in Tetrahymena thermophila, Danio rerio and C. elegans, we showed that MEC-17 is an α-tubulin acetyltransferase whose function is conserved among diverse species. Surprisingly, the catalytic activity of MEC-17 as an acetyltransferase for the K40 residue of the -tubulin expressed in the touch receptor neurons, MEC-12, is not required for touch sensation. C.elegans touch receptor neurons are filled with wide diameter microtubules with 15 protofilaments that were suggested to be specifically adapted for touch sensation. Other groups showed that the enzymatic function of MEC-17 is not required for touch sensation. We used a suppressor strategy to explore the role of MEC-17 in touch sensation. We identified sma-2 as a suppressor of mec-17 mediated touch insensitivity. sma-2 encodes a receptor activated SMAD in the TGF β pathway in C.elegans that plays a critical role in the regulation of body size. Using a mutant in another pathway that contributes to size regulation in C.elegans, we show that touch insensitivity in mutants with severe microtubule defects can be rescued by making the animal smaller, presumably because the axon of the touch receptor neuron is shorter. We also show that the suppression of microtubule defects by animal size reduction requires a functional mechanosensitive channel containing MEC-4. We propose that microtubules are needed for touch sensation when the axon reaches a certain length. Microtubules could play a role in connecting the individual ion channels, perhaps by making the membrane more rigid. Alternatively, microtubules could be required for propagation of the touch stimulus along the length of the axon to the synapse.