Congratulations to the Zhang lab for their recent paper published in Nature Structural & Molecular Biology titled “Cryo-EM structure of an active central apparatus.”
The central apparatus (CA) is the part of motile cilia that regulate ciliary beating. Accurately regulated ciliary beating is vital for various cellular activities required for nearly all eukaryotes. The CA, conserved across species, is an essential beating regulator consist of a pair of microtubules (C1 and C2) associated with hundreds of protein subunits per repeating units. Even though motile cilia play a central role in biology, the structure and exact protein composition of these cilia are largely unknown.
The new paper by L. Han et al. addresses critical gaps in the mechanistic understanding of the CA by determining the cryo-EM structure of a near-complete repeating unit of the CA from Chlamydomonas reinhardtii. The findings in this paper create a structural framework for understanding the role of the central apparatus in cilia and also will provide important guidance for better design of future studies exploring the roles of the human CA in ciliopathies.
This high-resolution structure provides critical insights into CA assembly and the roles of CA in ciliary-beating regulation. Through this structure, the Zhang lab reveals many interesting features of the CA composition and assembly, such as the clustering of CA projection proteins onto a spring-shaped scaffold mainly composed of the armadillo-repeat protein PF16. Their structure also uncovers that each projection complex contains a rachis-like protein that plays a central role in organizing all other subunits.
Most importantly, the Zhang lab captured the kinesin-like protein (KPL1) lined up in an array on the C2 microtubule and also captured the array in two different stepping states which likely correlate with beating wave propagation of cilia, providing a possible explanation of the CA’s regulatory role. This is a fundamentally different perspective of the role of the CA in ciliary beating. The CA has long been regarded as a passive complex molecular machine that simply provides mechanical feedback to the minus-end-directed dynein motor system in cilia. In this latest research article, by providing direct structural evidence in atomic details, the Zhang lab clearly shows that the CA serves as a fully active motor system, driven by the plus-end-directed kinesin motors. How these motor systems remotely communicate and coordinate with each other remains an important question for future investigation.
This study was led by co-first authors Long Han, Qinhui Rao, Renbin Yang, Yue Wang, Pengxin Chai and can be found on the Nature Press website: https://www.nature.com/articles/s41594-022-00769-9
Some of the authors’ key findings have been highlighted by Profs. Zehr and Roll-Mecak in their view article co-published in NSMB: https://www.nature.com/articles/s41594-022-00778-8
Another paper relevant to this work from the Zhang lab focusing on the outer-arm dynein was also recently published in NSMB: https://www.nature.com/articles/s41594-021-00656-9
By Jake Thrasher