SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans

Zhang Y, Yan L, Zhou Z, Yang P, Tian E, Zhang K, Zhao Y, Li Z, Song B, Han J, Miao L, Zhang H (2009). Cell 136: 308-21.

Speaker: Hsuan-Yun Hu (胡瑄耘)                                  Time: 13:00~14:00 May. 13, 2009

Commentator: Dr. Yee-Shin Lin (林以行老師)               Place: Room 601

Abstract:

Autophagy is a cellular mechanism responsible for the degradation of long-lived proteins, damaged organelles and accumulation of protein aggregates. Recently studies show that autophagy involves in many physiological processes, including animal development, nervous system function, aging, innate and adaptive immunity. Many studies use C. elegans as an animal model to study the role of autophagic mechanisms in the physiological processes [1]. Germ cells specifically possess germ granules, called P granules in worms and are believed to regulate germ cell fates [2]. The components of P granules include RNA and numerous proteins. Among those proteins, PGL and GLH proteins accompany with P granules at all stages. During the early embryogenesis of C. elegans, germline P granules are only found in germ cells through four asymmetric divisions. However, the mechanism of P granules depletion in somatic cells is not known. In this paper, the authors find that in autophagy mutants, P granule components PGL-1 and PGL-3 are accumulated into aggregates, termed PGL granules in somatic cells. By immunoelectron microscopy (immunoEM) study, they observed that PGL-1 was located in membrane-surrounded structures, which are similar to autophagolysosomes in somatic cells. It strengthens the evidence that P granule components in somatic cells are degraded by autophagy. Further, they find that sepa-1 (suppressor of ectopic P granule in autophagy mutants) is essential for the accumulation of PGL-1 and PGL-3 into PGL granules and it is also involved in the clearance of maternally derived P granules components in somatic cells. SEPA-1 directly binds to PGL-3 and to the autophagy protein LGG-1/ATG8. It suggests that SEPA-1 acts as an adaptor protein in linking PGL granule components to the autophagic machinery. In summary, during the embryogenesis of C. elegans, autophagy selectively degrades P granules mediated by SEPA-1 in somatic cells. This study reveals a specific physiological function of selective autophagic degradation during animal development.

References:

1.          E.V. Megalou, N. Tavernarakis, Autophagy in Caenorhabditis elegans, Biochim. Biophys. Acta (2009), doi:10.1016/j. bbamcr.2008.12.010

2.          Strome S, Lehmann R (2007). Germ versus soma decisions: lessons from flies and worms. Science 316: 392-3.