[PMID]: | 28910396 |
[Au] Autor: | Merrill NM; Schipper JL; Karnes JB; Kauffman AL; Martin KR; MacKeigan JP |
[Ad] Endereço: | Van Andel Institute Graduate School, Grand Rapids, Michigan, United States of America. |
[Ti] Título: | PI3K-C2α knockdown decreases autophagy and maturation of endocytic vesicles. |
[So] Source: | PLoS One;12(9):e0184909, 2017. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Phosphoinositide 3-kinase (PI3K) family members are involved in diverse cellular fates including cell growth, proliferation, and survival. While many molecular details are known about the Class I and III PI3Ks, less is known about the Class II PI3Ks. To explore the function of all eight PI3K isoforms in autophagy, we knock down each gene individually and measure autophagy. We find a significant decrease in autophagy following siRNA-mediated PIK3C2A (encoding the Class 2 PI3K, PI3K-C2α) knockdown. This defective autophagy is rescued by exogenous PI3K-C2α, but not kinase-dead PI3K-C2α. Using confocal microscopy, we probe for markers of endocytosis and autophagy, revealing that PI3K-C2α colocalizes with markers of endocytosis. Though endocytic uptake is intact, as demonstrated by transferrin labeling, PIK3C2A knockdown results in vesicle accumulation at the recycling endosome. We isolate distinct membrane sources and observe that PI3K-C2α interacts with markers of endocytosis and autophagy, notably ATG9. Knockdown of either PIK3C2A or ATG9A/B, but not PI3KC3, results in an accumulation of transferrin-positive clathrin coated vesicles and RAB11-positive vesicles at the recycling endosome. Taken together, these results support a role for PI3K-C2α in the proper maturation of endosomes, and suggest that PI3K-C2α may be a critical node connecting the endocytic and autophagic pathways. |
[Mh] Termos MeSH primário: |
Biomarcadores/metabolismo Endossomos/metabolismo Fosfatidilinositol 3-Quinases/genética Vesículas Transportadoras/metabolismo
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[Mh] Termos MeSH secundário: |
Autofagia Linhagem Celular Proliferação Celular Endocitose Técnicas de Silenciamento de Genes Seres Humanos Fosfatidilinositol 3-Quinases/metabolismo RNA Interferente Pequeno/metabolismo Transdução de Sinais
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Biomarkers); 0 (RNA, Small Interfering); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (PIK3C2A protein, human) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171012 |
[Lr] Data última revisão:
| 171012 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170915 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0184909 |
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