The miR-199/DNM regulatory axis controls receptor-mediated endocytosis

  1. Aranda, Juan F. 12
  2. Canfrán-Duque, Alberto 12
  3. Goedeke, Leigh 12
  4. Suárez, Yajaira 12
  5. Fernández-Hernando, Carlos 12
  1. 1 Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  2. 2 Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA
Revista:
Journal of Cell Science

ISSN: 1477-9137,  0021-9533

Año de publicación: 2015

Volumen: 128

Número: 17

Páginas: 3197–3209.

Tipo: Artículo

DOI: 10.1242/JCS.165233 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Journal of Cell Science

Resumen

Small non-coding RNAs (microRNAs) are important regulators of gene expression that modulate many physiological processes; however, their role in regulating intracellular transport remains largely unknown. Intriguingly, we found that the dynamin (DNM) genes, a GTPase family of proteins responsible for endocytosis in eukaryotic cells, encode the conserved miR-199a and miR-199b family of miRNAs within their intronic sequences. Here, we demonstrate that miR-199a and miR-199b regulate endocytic transport by controlling the expression of important mediators of endocytosis such as clathrin heavy chain (CLTC), Rab5A, low-density lipoprotein receptor (LDLR) and caveolin-1 (Cav-1). Importantly, miR-199a-5p and miR-199b-5p overexpression markedly inhibits CLTC, Rab5A, LDLR and Cav-1 expression, thus preventing receptor-mediated endocytosis in human cell lines (Huh7 and HeLa). Of note, miR-199a-5p inhibition increases target gene expression and receptor-mediated endocytosis. Taken together, our work identifies a new mechanism by which microRNAs regulate intracellular trafficking. In particular, we demonstrate that the DNM, miR-199a-5p and miR-199b-5p genes act as a bifunctional locus that regulates endocytosis, thus adding an unexpected layer of complexity in the regulation of intracellular trafficking.

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Información de financiación

Financiadores

  • National Institutes of Health United States
    • R01HL107953
    • R01HL106063
    • 1F31AG043318

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