SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans.
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.
Zhang
Yuxia
Y
National Institute of Biological Sciences, Beijing 102206, P.R. China.
Yan
Libo
L
Zhou
Zhi
Z
Yang
Peiguo
P
Tian
E
E
Zhang
Kai
K
Zhao
Yu
Y
Li
Zhipeng
Z
Song
Bing
B
Han
Jinghua
J
Miao
Long
L
Zhang
Hong
H
D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D012734:Disorders of Sex Development; D005111:Extrachromosomal Inheritance; D008297:Male; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C534959:PGL-3 protein, C elegans; D016601:RNA-Binding Proteins; C534958:SEPA-1 protein, C elegans