Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation

Intraflagellar transport for ciliary assembly and maintenance is driven by dynein and kinesins specific to the cilia. It has been shown that anterograde and retrograde transports run on different regions of the doublet microtubule, i.e., separate train tracks. However, little is known about the regulatory mechanism of this selective process. Since the doublet microtubule is known to display specific post-translational modifications of tubulins, i.e., tubulin code, for molecular motor regulations, we investigated the motility of ciliary specific dynein-2 under different post-translational modification by coarse-grained molecular dynamics. Our setup allows us to simulate the landing behaviors of dynein-2 on un-modified, detyrosinated, poly-glutamylated and poly-glycylated microtubules in silico. Our study revealed that poly-glutamylation can play an inhibitory effect on dynein-2 motility. Our result indicates that poly-glutamylation of the B-tubule of the doublet microtubule can be used as an efficient means to target retrograde intraflagellar transport onto the A-tubule.

Automated summary

Intraflagellar transport in ciliary assembly and maintenance is driven by specific dynein and kinesins. Anterograde and retrograde transports occur on different regions of the microtubule. The regulatory mechanism of this selective process is not well understood. We simulated the motility of ciliary-specific dynein-2 under different post-translational modifications and found that poly-glutamylation can inhibit dynein-2 motility. This suggests that poly-glutamylation of the B-tubule can target retrograde transport onto the A-tubule.