MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy.
J Cell Biol
; 215(5): 667-685, 2016 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-27872138
ABSTRACT
Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy, the lysosome-based catabolic process, involve vesicular biogenesis (early stage) and turnover (end stage). Much is known about early-stage events; however, our understanding of how the end stages of these processes are governed is incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family, which is preferentially expressed in the stem cell-enriched limbal epithelium, coordinately regulates aspects of both these activities. Loss of miR-103/107 causes dysregulation of macropinocytosis with the formation of large vacuoles, primarily through up-regulation of Src, Ras, and Ankfy1. Vacuole accumulation is not a malfunction of early-stage autophagy; rather, miR-103/107 ensure proper end-stage autophagy by regulating diacylglycerol/protein kinase C and cyclin-dependent kinase 5 signaling, which enables dynamin to function in vacuole clearance. Our findings unveil a key biological function for miR-103/107 in coordinately suppressing macropinocytosis and preserving end-stage autophagy, thereby contributing to maintenance of a stem cell-enriched epithelium.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Pinocitose
/
Autofagia
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MicroRNAs
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2016
Tipo de documento:
Article