NIH Research Festival
Cells functionalize microtubules with spatiotemporally complex patterns of posttranslational modifications. How effectors interpret this tubulin modification code is largely unknown. Here, we show that katanin, a microtubule severing AAA ATPase mutated in microcephaly and critical for cell division, axonal elongation and cilia biogenesis, responds precisely, differentially and combinatorially to three chemically distinct modifications: glycylation, glutamylation, and tyrosination, but is insensitive to tubulin acetylation. Glutamylation and glycylation act as antagonistic rheostats with glycylation being protective of microtubules. Katanin exhibits graded and divergent responses to glutamylation on the Œ±- and Œ≤-tubulin tails, and these act combinatorially. The structure of the katanin hexamer central pore constrains the polyglutamate chain patterns on Œ≤-tails that can productively be recognized. In contrast, elements distal to the katanin AAA core sense Œ±-tubulin tyrosination, and detyrosination downregulates severing. The multivalent microtubule recognition that enables katanin to read multiple tubulin modification inputs explains in vivo observations and illustrates how effectors can integrate tubulin code signals to produce diverse functional outcomes.
Scientific Focus Area: Molecular Biology and Biochemistry
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