title: Self-eating to remove cilia roadblock.
abstract: Autophagy delivers many proteins and cellular components to the lysosome for degradation via selective or nonselective mechanisms. By controlling the stability of defined protein factors, autophagy might regulate cellular processes in a precise and finely-tuned manner. In this study, we demonstrated that autophagy positively regulates the biogenesis of the primary cilium, an antenna-like organelle that senses the environment and transduces signals. Defects in the function or structure of cilia cause a number of human diseases called "ciliopathies." We found that the autophagosome membrane anchored protein LC3 interacts with OFD1 (oral-facial-digital syndrome 1) and removes it from the centriolar satellite upon serum starvation to initiate primary cilium biogenesis. OFD1 regulation and primary cilium formation are defective in autophagy-deficient cells, and reducing OFD1 protein levels through RNA interference rescues primary cilium formation. More strikingly, knockdown of OFD1 induces primary cilium formation in unstressed cells as well as in a human breast cancer cell that was previously reported to have lost the ability to form primary cilia. These findings therefore suggest an unexpected link among autophagy, ciliogenesis, ciliopathy, and cancers.
authors.affiliation: College of Life Sciences; Zhejiang University; Hangzhou, China; Center for Autophagy Research; Department of Internal Medicine; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Tang
authors.affiliation: College of Life Sciences; Zhejiang University; Hangzhou, China.
authors.forename: Muyuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Center for Autophagy Research; Department of Internal Medicine; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics* / Q000502:physiology*; D045744:Cell Line, Tumor; D002923:Cilia; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C115130:OFD1 protein, human; D011506:Proteins
keywords: OFD1; PCM1; autophagy; centriolar satellites; primary ciliogenesis