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Article Abstract
The primary cilium plays a crucial function in sensing and transmitting extracellular signals into cells. The initiation of ciliogenesis hinges on the recruitment of Tau tubulin kinase 2 (TTBK2) to the distal appendages (DAs) of centrioles through CEP164. However, the detailed mechanism underlying the CEP164/TTBK2 interaction at DAs during ciliogenesis remains incompletely understood. In this study, we unveil that CEP164 features a long intrinsically disordered region and forms dynamic condensates with TTBK2 through phase separation. Our investigation demonstrates that CEP164 undergoes phase separation with TTBK2 through multivalent electrostatic interactions. These interactions facilitate the efficient recruitment of TTBK2 to DAs, thereby kickstarting the process of cilia formation. Therefore, our findings provide insights into the molecular regulation of CEP164/TTBK2 interactions at DAs and highlight the pivotal role of phase separation in promoting cilia formation.
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| http://dx.doi.org/10.1016/j.celrep.2025.115810 | DOI Listing |
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