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Review
. 2016 Apr:39:1-7.
doi: 10.1016/j.ceb.2016.01.008. Epub 2016 Jan 27.

Autophagy and primary cilia: dual interplay

Olatz Pampliega  1 , Ana Maria Cuervo  2
Affiliations
Review

Autophagy and primary cilia: dual interplay

Olatz Pampliega et al. Curr Opin Cell Biol. 2016 Apr.

Abstract

Primary cilia are microtubule-based organelles for sensing of the extracellular milieu and transducing this information into the cell through a variety of molecular signaling pathways. Functioning of the primary cilium has been recently connected to autophagy, a pathway for degradation of cellular components in lysosomes. Autophagy regulates the length of the cilia by removing proteins required for ciliogenesis, a phenomenon that is molecularly different if performed by basal autophagy or when autophagy is induced in response to various stressors. Here we review the current knowledge about the dual interaction between autophagy and ciliogenesis, and discuss the potential role that deregulated ciliary autophagy could have in pathologies with alterations in autophagy and ciliogenesis.

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Figures

Figure 1
Figure 1. Molecular interaction between of autophagy and ciliogenesis
Growth of primary cilia (PC) from the mother centriole is attained through continuous bidirectional intraflagellar trafficking (IFT) of proteins such as IFT20. Ciliogenesis is prevented by OFD1, a repressor that localizes at the distal appendages of the mother centriole (capping of the distal appendages by OFD1 is shown in the right boxed area). Activation of ciliogenesis or ciliary Hedgehog signaling induces autophagy. During activation of autophagy, autophagy related proteins (ATG) proteins organize into functional complexes to form a preautophagosome membrane, which surrounds the cargo and then seals into double membrane vesicles (autophagosomes). Autophagosome content is degraded upon fusion with lysosomes. In ciliary-induced autophagy, the pre-autophagosomal marker ATG16L1 trafficks in IFT20-containing vesicles to the ciliary base, where autophagosomes may form from either the plasma membrane or the ciliary pocket.
Figure 2
Figure 2. The complex role of autophagy in the regulation of ciliogenesis
Autophagy has been shown both to enhance and to decrease ciliogenesis. This contrasting effect may depend on the cell type, cellular conditions and likely also on the type of autophagy and the cargo targeted by the autophagic process. Based on the published studies reporting autophagic degradation of both ciliogenesis inhibitors (such as OFD1) and activators (such as IFT20, IFT88 and likely also PCM1) we propose that changes in the ratio of degradation by autophagy of these two pool of regulators could determine the final ciliogenesis rate.
Figure 3
Figure 3. Human diseases in the crossroad between primary cilia and autophagy
Malfunction of both motile cilia (MC) and primary cilia (PC) in different pathological conditions has been recently connected to autophagy. Top left: scanning electron microscopy of primary cilia in mouse embryonic fibroblasts. Bottom left: Autophagy has been shown to contribute to shortening of MC in chronic obstructive respiratory disease (COPD) through HDAC-mediated degradation of intraflagellar (IFT) proteins required for ciliary growth and function. Cigarette smoke triggers this event by inducing global polyubiquitination. Right: Autophagy may contribute to the abnormally long PC observed in polycystic kidney disease (PKD) (top) and Huntington’s disease (HD) (bottom). In PKD, the observed exacerbation of TORC1 signaling may repress degradation of ciliary components by autophagy such as IFT20 and maybe PCM1, and contribute to enhanced ciliogenesis. In the case of HD, ciliary malfunction may originate from the disruption in the patients of the dual role of huntingtin (Htt) in selective autophagy and trafficking of ciliogenesis regulators, such as PCM1.
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References

    1. Zhang H, Baehrecke EH. Eaten alive: Novel insights into autophagy from multicellular model systems. Trends in cell biology. 2015;25(7):376–387. - PMC - PubMed
    1. Mizushima N. The pleiotropic role of autophagy: From protein metabolism to bactericide. Cell Death Differ. 2005;12:1535–1541. - PubMed
    1. Choi AMK, Ryter SW, Levine B. Autophagy in human health and disease. New England Journal of Medicine. 2013;368(7):651–662. - PubMed
    1. Shen HM, Mizushima N. At the end of the autophagic road: An emerging understanding of lysosomal functions in autophagy. Trends in biochemical sciences. 2014;39(2):61–71. - PubMed
    1. Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol. 2015;16(8):461–472. - PubMed

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