Mystery Unraveled: Control of Centriole Amplifications in Multiciliate Cells

Cilium is a hair-like organelle formed on a specialized centriole. Multicilia are abundant in epithelial tissues such as brain ventricle, trachea, and oviduct, important for luminal flow, tissue surface moisturization and cleanup, or germ cell movement. In proliferating cells, one mother centriole is allowed to only produce one “daughter” per cell cycle. Multicilia formation, however, can require hundreds of centrioles. Electron microscopy has long revealed that not only can a mother herein generate multiple daughters but many ring-like structures called deuterosomes also function as “cradles” for de novo centriole formation. How deuterosome functions, however, remains unclear.

PhD student ZHAO Huijie and his colleagues, supervised by Dr. ZHU Xueliang and Dr. YAN Xiumin from State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, SIBS, CAS, find that the mother centriole-dependent (MCD) and deuterosome-dependent (DD) centriole biogenesis pathways are respectively controlled by Cep63, a known mother centriole protein, and its uncharacterized paralog, Deup1. Deup1 decorates deuterosomes in multiciliating mouse tracheal epithelial cells (Figure 1a) and is essential for deuterosome assembly. Like Cep63 to mother centriole, Deup1 recruits Cep152 and Plk4 to deuterosomes to activate centriole biogenesis (Figure 1b). Deup1 diverged from Cep63 in a common ancestor of lobe-finned fish and tetrapod, correlated with dense multicilia formation, an event possibly contributing to the land adaption of vertebrate during evolution. Therefore, Deup1 enables formation of centriole biogenic “cradles” in large quantities in mother centriole-independent manner for massive centriole biogenesis during multiciliation. Such a mechanism also permits non-multicliate cells to stick to the MCD pathway by simply silencing Deup1 expression.

This work, entitled “The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis”, was published online in Nature Cell Biology on November 17, 2013. It was supported by grants from CAS, MOST, NSFC, and Shanghai Municipal Science and Technology Commission.

Fig1. Deuterosome localization of Deup1 (a) and proposed model (b). (Image by Dr. ZHU Xueliang’s group)