Tubulin polyglutamylation regulates axonemal motility by modulating activities of inner-arm dyneins.
Tubulin polyglutamylation is a modification that adds multiple glutamates to the gamma-carboxyl group of a glutamate residue in the C-terminal tails of alpha- and beta-tubulin [1, 2]. This modification has been implicated in the regulation of axonal transport and ciliary motility. However, its molecular function in cilia remains unknown. Here, using a novel Chlamydomonas reinhardtii mutant (tpg1) that lacks a homolog of human TTLL9, a glutamic acid ligase enzyme [3], we found that the lack of a long polyglutamate side chain in alpha-tubulin moderately weakens flagellar motility without noticeably impairing the axonemal structure. Furthermore, the double mutant of tpg1 with oda2, a mutation that leads to loss of outer-arm dynein, completely lacks motility. More surprisingly, when treated with protease and ATP, the axoneme of this paralyzed double mutant displayed faster microtubule sliding than the motile oda2 axoneme. These and other results suggest that polyglutamylation directly regulates microtubule-dynein interaction mainly by modulating the function of inner-arm dyneins.
Kubo
Tomohiro
T
Department of Biological Science, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.
Yanagisawa
Haru-aki
HA
Yagi
Toshiki
T
Hirono
Masafumi
M
Kamiya
Ritsu
R
D000818:Animals; D056444:Axonemal Dyneins / Q000378:metabolism*; D016825:Chlamydomonas reinhardtii / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D009154:Mutation; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011099:Polyglutamic Acid / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D011099:Polyglutamic Acid; D056444:Axonemal Dyneins; D010453:Peptide Synthases; C112698:tubulin polyglutamylase