On November 18th, the international academic journal Nature Cell Biology published the research paper The Cep63 paralog Deup1 enables massive de novo centriole biogenesis online by the research team of Zhu Xueliang, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences for vertebrate multiciliogenesis. The result found that in higher animals, a pair of homologous proteins Deup1 and Cep63 regulate the two types of centromeric amplification methods of "from scratch" and "maternal centrosome-dependent" in the process of multicilia formation, and their The connection between the adaptation and evolution of vertebrates from the ocean to the land. This paper will also serve as the cover paper of the magazine.
The centromere is a barrel-shaped organelle composed of nine groups of triplet microtubules, mainly present in animal cells, and functions as a matrix of the centrosome or ciliary base. The centrosome usually contains a pair of centrosomes, which are the microtubule tissue centers of animal cells and serve as the poles of the spindle during cell division. The production of centrioles generally depends on the "mother" centromeres, and the "one-child" system is strictly implemented in the cell division cycle, that is, each "mother" centromere produces only one "child" centromere to avoid abnormal cell division And ensure that each daughter cell after division inherits a centrosome. Cilia are a kind of microtubule-rich hairy organelles, which can be called "moving cilia", which are the moving organs of cells and even individuals, and have appeared in protozoan flagellates and ciliates; "Cilia" are important receptors that can sense external stimuli such as sound, light, smell, and signal molecules. A large number of multi-ciliated cells are distributed on the surface of trachea, ventricle, fallopian tube and other tissues of higher animals, each of which can contain up to hundreds of kinetic cilia. Therefore, it is an interesting and important scientific question where the large number of centrosomes required by these multi-ciliated cells come from.
As early as in the 1960s and 1970s, scientists observed through an electron microscope that during the occurrence of multi-cilia, the mother centromere broke the "one-child system." More interestingly, centrioles are also formed around many ring structures called deuterosome (pronounced "cradle body"), and most of the centrioles are based on this kind of mother-neutral (and therefore Called "from scratch"). However, decades have passed, and the molecular composition and mechanism of action of the cradle are almost unknown.
Zhao Xuejie, a graduate student in the Zhu Xueliang research group, and Yan Xiumin, an associate researcher, used techniques such as ultra-high-resolution fluorescence microscopy and electron microscopy to discover that in the process of inducing mouse tracheal epithelial cells to differentiate into multiciliated cells in vitro, a protein they named Deup1 It is the key component of cradle body formation. Deup1 is not only necessary for the formation of cradle bodies in multi-ciliated cells, exogenous expression in ordinary cells can also induce the formation of cradle bodies and the occurrence of centrosomes from scratch, and even expression in bacteria can also form cradle bodies. Ring structure. Deup1 is a known homolog of the mother centromere protein Cep63. The latter shows a circular position on the mother centromere and can recruit Cep152 and Plk4 in sequence to form a "cradle" of the mother centromere with "child" centromeres. ".
They found that Deup1 also formed a "cradle" of centromeres through a similar mechanism. Therefore, they believe that Cep63 produces Deup1 through its gene replication and evolution, so that the cradle of centromeres can be assembled in a large amount in a manner that does not depend on the parent centromere, in order to rapidly expand the centromere. The beauty of this mechanism is that the organism can not only meet the demand for a large number of centrioles by multicilia cells by switching the expression of Deup1, but also ensure that other types of cells are only produced in a highly controllable maternal centrosome-dependent manner The new centromere prevents these cells from causing cell division and other abnormalities due to excessive centromere.
In addition, molecular evolutionary tree analysis suggests that Deup1 appears in tetrapods and their fish ancestors (meat-finned fish), in other bony fish (radial-finned fish) and more primitive chordates (such as Wenchang fish, ascidians) Does not exist. Correspondingly, the cells of radial finfish (such as zebrafish) also lack dense cilia. Therefore, in the evolution of vertebrates, the appearance of Deup1 is likely to enhance the ability of cilia to maintain the moist and clean surface of tissues such as trachea, increase the cilia density of cells, form cerebrospinal fluid flow, and promote egg movement. Adaptability and evolution to the terrestrial environment.
This subject is supported by the pilot project of the Chinese Academy of Sciences Stem Cell, the National Ministry of Science and Technology Major Research Program, the National Natural Science Foundation of China and the Shanghai Municipal Science and Technology Commission.
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