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

Masaki Saito, Wataru Otsu, Kuo Shun Hsu, Jen Zen Chuang, Teruyuki Yanagisawa, Vincent Shieh, Taku Kaitsuka, Fan Yan Wei, Kazuhito Tomizawa, Ching Hwa Sung

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1460-1472
Number of pages13
JournalEMBO Reports
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 1 2017
Externally publishedYes

Keywords

  • branched actin dynamics
  • Cdc42
  • clathrin-dependent endocytosis
  • primary ciliary resorption
  • Tctex-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Saito, M., Otsu, W., Hsu, K. S., Chuang, J. Z., Yanagisawa, T., Shieh, V., Kaitsuka, T., Wei, F. Y., Tomizawa, K., & Sung, C. H. (2017). Tctex-1 controls ciliary resorption by regulating branched actin polymerization and endocytosis. EMBO Reports, 18(8), 1460-1472. https://doi.org/10.15252/embr.201744204