MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement.

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement.
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MAP9/MAPH-9 支持轴丝微管双联体并调节运动。

DOI:
10.1101/2023.02.23.529616
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发表时间:
2023
期刊:
bioRxiv : the preprint server for biology
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作者:
Tran,MichaelV;Ferguson,JamesW;Cote,LaurenE;Khuntsariya,Daria;Fetter,RichardD;Wang,JenniferT;Wellard,StephenR;Sallee,MariaD;Genova,Mariya;Eskinazi,Sani;Magiera,MariaM;Janke,Carsten;Stearns,Tim;Lansky,Zdenek;Shen,Kang;M

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微管双管(MTDs)包括附着在完整圆柱形微管侧面的不完整微管(b管)。这些复合微管保存在整个生命树的纤毛中;然而,MTDs在体内形成和维持的机制仍然知之甚少。在这里,我们鉴定微管相关蛋白9 (MAP9)为mtd相关蛋白。我们证明了c。elegansMAPH-9是MAP9的同源物,在MTD组装过程中存在,并且只定位于MTD,这种偏好部分是由微管蛋白多谷氨酰化介导的。我们发现MAPH-9的缺失导致MTD超微结构缺陷,包括缩短和/或压扁b小管,原丝数量减少,轴突运动速度失调,纤毛功能紊乱。由于我们在培养的哺乳动物细胞和小鼠组织中发现哺乳动物同源基因MAP9定位于轴突,我们提出MAP9/MAPH-9在调节纤毛运动和支持轴突MTDs结构中起保守作用。
Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintainedin vivoremain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate thatC. elegansMAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs.
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