Tctex‐1 controls ciliary resorption by regulating branched actin polymerization and endocytosis

Abstract

The primary cilium is a plasma membrane‐protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin‐rich, endocytosis‐active periciliary subdomain. Furthermore, Tctex‐1, originally identified as a cytoplasmic dynein light chain, has a dynein‐independent role in ciliary resorption upon phosphorylation at Thr94. Here, we show that the remodeling and endocytosis of the ciliary pocket membrane are accelerated during ciliary resorption. This process depends on phospho(T94)Tctex‐1, actin, and dynamin. Mechanistically, Tctex‐1 physically and functionally interacts with the actin dynamics regulators annexin A2, Arp2/3 complex, and Cdc42. Phospho(T94)Tctex‐1 is required for Cdc42 activation before the onset of ciliary resorption. Moreover, inhibiting clathrin‐dependent endocytosis or suppressing Rab5GTPase on early endosomes effectively abrogates ciliary resorption. Taken together with the epistasis functional assays, our results support a model in which phospho(T94)Tctex‐1‐regulated actin polymerization and periciliary endocytosis play an active role in orchestrating the initial phase of ciliary resorption. image Ciliary resorption is causally linked to the G 1 ‐S transition during the cell cycle. This study shows that Tctex‐1 phosphorylated at Thr94 triggers actin polymerization and periciliary endocytosis required for the initial phase of ciliary resorption. Ciliary pocket membrane endocytosis is increased during ciliary resorption. The actin regulators Cdc42, Arp2/3 and annexin 2 are downstream effectors of phospho(T94)Tctex‐1 in ciliary resorption. Tctex‐1‐regulated clathrin‐mediated endocytosis is actively involved in ciliary resorption.