TY - JOUR
T1 - MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy
AU - Park, Jong Kook
AU - Peng, Han
AU - Katsnelson, Julia
AU - Yang, Wending
AU - Kaplan, Nihal
AU - Dong, Ying
AU - Rappoport, Joshua Z.
AU - He, Cong Cong
AU - Lavker, Robert M.
N1 - Funding Information:
Lentiviral constructs were obtained from the Northwestern University Skin Disease Research Center (NU-SDRC) DNA/RNA Delivery Core Facility and the NU-SDRC Morphology and Phenotyping Core Facility assisted in morphological analysis. The NU-SDRC is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR057216. This research is supported by National Institutes of Health grants EY06769, EY017539, and EY019463 (to R.M. Lavker) and DK094980 (to C.C. He); National Natural Science Foundation of China grant 31300814 (to Y. Dong); a Dermatology Foundation research grant and Career Development Award (to H. Peng); and a MidWest Eye Bank research grant (to H. Peng).
Publisher Copyright:
© Park et al.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201604032
DO - 10.1083/jcb.201604032
M3 - Article
C2 - 27872138
AN - SCOPUS:85008870932
SN - 0021-9525
VL - 215
SP - 667
EP - 685
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -