Eyeing autophagy and macropinocytosis in the corneal/limbal epithelia

Macroautophagy/autophagy is vital for cellular homeostasis and helps cells respond to various stress situations. Macropinocytosis enables cells to nonselectively engulf and take up large volumes of fluid and is known to supply amino acids to cells. The stem cell-enriched limbal epithelium has the machinery necessary to carry out both autophagy and macropinocytosis; however, both processes are relatively understudied in this tissue. We have demonstrated that these processes are linked via MIR103-MIR107, a microRNA family that is limbal epithelial-preferred. Loss of MIR103-MIR107 causes the accumulation of large vacuoles that originate, in part, from a dysregulation in macropinocytosis via activation of SRC-RAS signaling. We found that these vacuoles were autophagic in nature and retained in cells due to inappropriate regulation of end-stage autophagy. Specifically, MIR103-MIR107 regulates diacylglycerol-PRKC/protein kinase C and CDK5 (cyclin dependent kinase 5) signaling, which enables DNM1 (dynamin 1) to function in vacuole clearance.