Ruehle Marisa D, Li Sam, Agard David A, Pearson Chad G
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
bioRxiv. 2023 Nov 28:2023.11.17.567593. doi: 10.1101/2023.11.17.567593.
Basal bodies (BBs) are conserved eukaryotic structures that organize motile and primary cilia. The BB is comprised of nine, cylindrically arranged, triplet microtubules (TMTs) that are connected to each other by inter-TMT linkages which maintain BB structure. During ciliary beating, forces transmitted to the BB must be resisted to prevent BB disassembly. Poc1 is a conserved BB protein important for BBs to resist ciliary forces. To understand how Poc1 confers BB stability, we identified the precise position of Poc1 binding in the BB and the effect of Poc1 loss on BB structure. Poc1 binds at the TMT inner junctions, stabilizing TMTs directly. From this location, Poc1 also stabilizes inter-TMT linkages throughout the BB, including the cartwheel pinhead and the inner scaffold. Moreover, we identify a molecular response to ciliary forces via a molecular remodeling of the inner scaffold, as determined by differences in Fam161A localization. Thus, while not essential for BB assembly, Poc1 promotes BB interconnections that establish an architecture competent to resist ciliary forces.
基体（BBs）是保守的真核生物结构，负责组织运动性纤毛和初级纤毛。基体由九个呈圆柱形排列的三联体微管（TMTs）组成，这些微管通过维持基体结构的TMT间连接相互连接。在纤毛摆动过程中，传递到基体的力必须被抵抗，以防止基体解体。Poc1是一种保守的基体蛋白，对基体抵抗纤毛力很重要。为了了解Poc1如何赋予基体稳定性，我们确定了Poc1在基体中的精确结合位置以及Poc1缺失对基体结构的影响。Poc1在TMT内部连接处结合，直接稳定TMTs。从这个位置，Poc1还稳定了整个基体中的TMT间连接，包括中心粒轮辐小头和内部支架。此外，我们通过内部支架的分子重塑确定了对纤毛力的分子反应，这由Fam161A定位的差异决定。因此，虽然Poc1对基体组装不是必需的，但它促进了基体的相互连接，从而建立了能够抵抗纤毛力的结构。
