SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans

National Institute of Biological Sciences, Beijing 102206, P.R. China.
Cell (Impact Factor: 32.24). 02/2009; 136(2):308-21. DOI: 10.1016/j.cell.2008.12.022
Source: PubMed


How autophagy, an evolutionarily conserved intracellular catabolic system for bulk degradation, selectively degrades protein aggregates is poorly understood. Here, we show that several maternally derived germ P granule components are selectively eliminated by autophagy in somatic cells during C. elegans embryogenesis. The activity of sepa-1 is required for the degradation of these P granule components and for their accumulation into aggregates, termed PGL granules, in autophagy mutants. SEPA-1 forms protein aggregates and is also a preferential target of autophagy. SEPA-1 directly binds to the P granule component PGL-3 and also to the autophagy protein LGG-1/Atg8. SEPA-1 aggregates consistently colocalize with PGL granules and with LGG-1 puncta. Thus, SEPA-1 functions as a bridging molecule in mediating the specific recognition and degradation of P granule components by autophagy. Our study reveals a mechanism for preferential degradation of protein aggregates by autophagy and emphasizes the physiological significance of selective autophagy during animal development.

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Available from: Kai Zhang, Nov 14, 2014
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    • "This targeting of RNA granules to the vacuole by autophagy was referred as " granulophagy " and may provide a mechanism for efficient PBs/SGs clearance, regulating their abundance during stress and development, serving in parallel as a means for the mass degradation of mRNA molecules that reside inside them (Buchan et al., 2013). A similar mechanism has been found to occur during C. elegans embryonic development, where germ-line specific mRNPs (P-granules) are selectively removed from somatic cells through autophagy (Zhang et al., 2009). "
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    • "LGG-2 RNAi treatment was lethal in mutants carrying a loss-of-function mutation in daf-2, the C. elegans insulin-like tyrosine kinase receptor that triggers constitutive dauer entry (Meléndez et al., 2003). Furthermore, LGG-2-depleted embryos accumulate P-granule components in the somatic cells (Zhang et al., 2009). In lgg-2(tm5755) mutant embryos, LGG-1 was still recruited around sperm organelles and appeared clustered in the early embryos (Manil-Ségalen et al., 2014). "
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    • "VBH-1 was also localized into large aggregates in both somatic and germline blastomeres during early embryogenesis after heat shock. The aggregates in somatic blastomeres are not P granules because these are asymmetrically inherited to the germline blastomeres and further disassembled and degraded through autophagy in somatic blastomeres [67], [68]. One important difference between the aggregates formed in the gonad and those observed in early embryos is that in the latter, VBH-1 did not perfectly overlap with CGH-1; however, these proteins are closely associated. "
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