Revealing the Mysterious Role of Myosin-Va in the Initial Step of Cilium Assembly— In a research article published in the January 15th of Nature Cell Biology, Dr. Tang K. Tang and his lab members at the Institute of Biomedical Sciences, Academia Sinica, uncover for the first time the role of Myosin-Va in the initial step of cilium assembly and reveal the underlying mechanism.
In a research article published in the January issue of the prestigious scientific journal Nature Cell Biology, Dr. Tang K. Tang (a Distinguished Research Fellow) and his lab members at the Institute of Biomedical Sciences (IBMS), Academia Sinica, uncover for the first time the role of Myosin-Va in the initial step of cilium assembly and reveal the underlying mechanism.
Primary cilia are microtubule-based organelles protruding from the apical cell surface to perform a wide variety of biological functions. Defects in cilium assembly cause a number of genetic disorders known as ciliopathies, which are characterized by loss of vision/hearing, disturbing kidney function, organ left-right displacement, and defects in brain development. Cilium assembly is a highly ordered process, which has been classified into the intracellular and the extracellular pathways, depended on cell types. At the very beginning of ciliogenesis, several small preciliary vesicles (PCVs) first appeared and transported to the distal appendage (DA) of the mother centriole (M-centriole), followed by fusing to form a large primary ciliary vesicle (CV). The axoneme, a microtubule-based cytoskeleton, then grows and elongates within the CV, which later forms the ciliary sheath that surrounds the ciliary shaft. The ciliary shaft eventually becomes the ciliary membrane, while the ciliary sheath docks and fuses with the plasma membrane, allowing to protrude a cilium. Although, the structure and morphology of primary cilia has been well documented, the molecular basis that defines the onset of ciliogenesis remains mysterious.
This Nature Cell biology paper demonstrates that the myosin-Va-mediated transportation of preciliary vesicle to the M-centriole is the earliest event that defines the onset of ciliogenesis. The research team found that Myosin-Va is the earliest marker that first appears on PCV, CV, and ciliary sheath during ciliogenesis. Furthermore, Myosin-Va is required for the trafficking of PCVs to the mother centriole in ciliated cells using both the intracellular and the extracellular pathways, implying that this process is universal. Importantly, this paper uncovers molecular mechanisms of an uncharacterized initial step in cilium assembly. Myosin-Va mediates the transportation of PCVs to the centrosomal region surrounding the centrosome through a dynein- and microtubule-dependent pathway, followed by trafficking of myosin-Va-associated PCVs to the M-centriole via the centrosome-associated branched actin network. This important finding provides a molecular basis for in-depth understanding of cilium assembly and human ciliopathy.
The authors of this paper: Chien-Ting Wu, Hsin-Yi Chen, and Tang K. Tang.
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The full research article is available at
https://www.nature.com/articles/s41556-017-0018-7
This work was supported by Academia Sinica Award and the grant from the Ministry of Science and Technology, Taiwan.
Media Contacts:
Dr. Tang K. Tang, Institute of Biomedical Sciences, Academia Sinica
email: tktang@ibms.sinica.edu.tw;
(Tel) +886-2-2652-3901; (Fax) +886-2-2782-9143