Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cell Biol. 2016 Dec 5;215(5):667-685. Epub 2016 Nov 21.

MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy.

Author information

1
Department of Dermatology, Northwestern University, Chicago, IL 60611.
2
Rush Medical Center, Chicago, IL 60615.
3
Department of Ophthalmology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100048, China.
4
Center for Advanced Microscopy and Nikon Imaging Center, Northwestern University, Chicago, IL 60611.
5
Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611.
6
Department of Dermatology, Northwestern University, Chicago, IL 60611 r-lavker@northwestern.edu.

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.

PMID:
27872138
PMCID:
PMC5146999
DOI:
10.1083/jcb.201604032
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center