Microtubule asters anchored by FSD1 control axoneme assembly and ciliogenesis

Yu-Cheng Zhang,Guang Wang,Yan Huang,Xue-Min Zhang,Hui-Yan Li,Feng Liu,Yun-Feng Bai,Hai-Qing Tu,Yan Chang,Zeng-Qing Song,Min Wu,Zhi-Bin Liu,Tao Zhou,Xuan-He Qin,Qiu-Ying Han,Huai-Bin Hu,Ai-Ling Li

doi:10.1038/s41467-018-07664-2

Abstract

Defective ciliogenesis causes human developmental diseases termed ciliopathies. Microtubule (MT) asters originating from centrosomes in mitosis ensure the fidelity of cell division by positioning the spindle apparatus. However, the function of microtubule asters in interphase remains largely unknown. Here, we reveal an essential role of MT asters in transition zone (TZ) assembly during ciliogenesis. We demonstrate that the centrosome protein FSD1, whose biological function is largely unknown, anchors MT asters to interphase centrosomes by binding to microtubules. FSD1 knockdown causes defective ciliogenesis and affects embryonic development in vertebrates. We further show that disruption of MT aster anchorage by depleting FSD1 or other known anchoring proteins delocalizes the TZ assembly factor Cep290 from centriolar satellites, and causes TZ assembly defects. Thus, our study establishes FSD1 as a MT aster anchorage protein and reveals an important function of MT asters anchored by FSD1 in TZ assembly during ciliogenesis.

Highlights

Defective ciliogenesis causes human developmental diseases termed ciliopathies
To clarify how FSD1 facilitated the recruitment of transition zone (TZ) components to the mother centriole, we examined its relationship with Cep[290] and Cep[162], which had been reported to promote TZ assembly[52,54]
We further found that PCM1 depletion disrupted the recruitment of TZ proteins, including TMEM67 and NPHP8 (Fig. 4e, f and Supplementary Fig. 6h, i), supporting the possibility that Cep[290] at Centriolar satellites (CSs) might play an essential role in ciliary TZ assembly

Summary

Introduction

Defective ciliogenesis causes human developmental diseases termed ciliopathies. Microtubule (MT) asters originating from centrosomes in mitosis ensure the fidelity of cell division by positioning the spindle apparatus. Other proteins, including EB1, SSX2IP, Trichoplein, and CAP350/ FOP/CEP19, which are close to subdistal appendages of mother centrioles, have been shown to participate in MT aster anchoring possibly through Ninein[21,22,23,24,25,26]. All of these known anchoring proteins are required for ciliogenesis[27], suggesting that MT asters contribute to cilia assembly. How Cep[290] contributes to TZ assembly remains unclear

Methods

Results

Conclusion