Back to Search
Start Over
Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites
- Source :
- Nature. October 10, 2013, Vol. 502 Issue 7470, p254, 15 p.
- Publication Year :
- 2013
-
Abstract
- The primary cilium is a microtubule-based organelle that functions in sensory and signalling pathways. Defects in ciliogenesis can lead to a group of genetic syndromes known as ciliopathies (1-3). However, the regulatory mechanisms of primary ciliogenesis in normal and cancer cells are incompletely understood. Here we demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral-facial-digital syndrome 1), at centriolar satellites promotes primary cilium biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles and protein aggregates are engulfed in autophagosomes and delivered to lysosomes for destruction (4). We show that the population of OFD1 at the centriolar satellites is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient Atg5or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar satellites, leading to fewer and shorter primary cilia and a defective recruitment of BBS4 (Bardet-Biedl syndrome 4) to cilia. These defects are fully rescued by OFD1 partial knockdown that reduces the population of OFD1 at centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites promotes cilia formation in both cycling cells and transformed breast cancer MCF7 cells that normally do not form cilia. This work reveals that removal of OFD1 by autophagy at centriolar satellites represents a general mechanism to promote ciliogenesis in mammalian cells. These findings define a newly recognized role of autophagy in organelle biogenesis.<br />During autophagy, the membrane anchored LC3 (microtubule-associated protein 1 light chain 3, also known as MAP1LC3B) interacts with cargo and cargo-adaptor proteins, recruiting cargoes to the autophagosome for subsequent degradation [...]
- Subjects :
- Satellite DNA -- Physiological aspects -- Research
Cilia and ciliary motion -- Physiological aspects -- Genetic aspects -- Research
Autophagy (Cytology) -- Physiological aspects -- Genetic aspects -- Research
Environmental issues
Science and technology
Zoology and wildlife conservation
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 502
- Issue :
- 7470
- Database :
- Gale General OneFile
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.359732341