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EMBO Rep. 2017 Aug;18(8):1460-1472. doi: 10.15252/embr.201744204. Epub 2017 Jun 12.

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

Author information

1
Department of Molecular Pharmacology, Graduate School of Medicine, Tohoku University, Aoba-ku Sendai, Japan saimasa@med.tohoku.ac.jp chsung@med.cornell.edu.
2
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku Sendai, Japan.
3
Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, NY, USA.
4
Department of Molecular Pharmacology, Graduate School of Medicine, Tohoku University, Aoba-ku Sendai, Japan.
5
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
6
Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, NY, USA saimasa@med.tohoku.ac.jp chsung@med.cornell.edu.
7
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY, USA.

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.

KEYWORDS:

Cdc42; Tctex‐1; branched actin dynamics; clathrin‐dependent endocytosis; primary ciliary resorption

PMID:
28607034
PMCID:
PMC5538770
DOI:
10.15252/embr.201744204
[Indexed for MEDLINE]
Free PMC Article

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