MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy

Jong Kook Park, Han Peng, Julia Katsnelson, Wending Yang, Nihal Kaplan, Ying Dong, Joshua Z. Rappoport, Cong Cong He, Robert M. Lavker

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)667-685
Number of pages19
JournalJournal of Cell Biology
Volume215
Issue number5
DOIs
StatePublished - 2016

Fingerprint

Autophagy
MicroRNAs
Vacuoles
Stem Cells
Epithelium
Cyclin-Dependent Kinase 5
Diacylglycerol Kinase
Dynamins
Lysosomes
Protein Kinase C
Up-Regulation
Maintenance

ASJC Scopus subject areas

  • Cell Biology

Cite this

Park, J. K., Peng, H., Katsnelson, J., Yang, W., Kaplan, N., Dong, Y., ... Lavker, R. M. (2016). MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy. Journal of Cell Biology, 215(5), 667-685. https://doi.org/10.1083/jcb.201604032

MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy. / Park, Jong Kook; Peng, Han; Katsnelson, Julia; Yang, Wending; Kaplan, Nihal; Dong, Ying; Rappoport, Joshua Z.; He, Cong Cong; Lavker, Robert M.

In: Journal of Cell Biology, Vol. 215, No. 5, 2016, p. 667-685.

Research output: Contribution to journalArticle

Park, JK, Peng, H, Katsnelson, J, Yang, W, Kaplan, N, Dong, Y, Rappoport, JZ, He, CC & Lavker, RM 2016, 'MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy', Journal of Cell Biology, vol. 215, no. 5, pp. 667-685. https://doi.org/10.1083/jcb.201604032
Park JK, Peng H, Katsnelson J, Yang W, Kaplan N, Dong Y et al. MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy. Journal of Cell Biology. 2016;215(5):667-685. https://doi.org/10.1083/jcb.201604032
Park, Jong Kook ; Peng, Han ; Katsnelson, Julia ; Yang, Wending ; Kaplan, Nihal ; Dong, Ying ; Rappoport, Joshua Z. ; He, Cong Cong ; Lavker, Robert M. / MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy. In: Journal of Cell Biology. 2016 ; Vol. 215, No. 5. pp. 667-685.
@article{dd5cc32acf1449e799974aa149e0d607,
title = "MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy",
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.",
author = "Park, {Jong Kook} and Han Peng and Julia Katsnelson and Wending Yang and Nihal Kaplan and Ying Dong and Rappoport, {Joshua Z.} and He, {Cong Cong} and Lavker, {Robert M.}",
year = "2016",
doi = "10.1083/jcb.201604032",
language = "English (US)",
volume = "215",
pages = "667--685",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85008870932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008870932&partnerID=8YFLogxK

U2 - 10.1083/jcb.201604032

DO - 10.1083/jcb.201604032

M3 - Article

VL - 215

SP - 667

EP - 685

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -