Identification of unconventional endocytosis induced by actin depolymerization in mammary epithelial cells

Abstract

During the development of mammary gland, inner cells undergo clearance by programmed cell death, contributing to the lumen formation. However, suppression of apoptotic and non-apoptotic cell death fails to fully prevent luminal cell clearance. What other biological mechanisms are involved in lumen formation remains poorly understood. In this study, I found that acute actin disruption promotes inner cell clearance in mammary acini. Using cell suspension cultures, I observed unexpectedly that extracellular matrix-detached cells induce formation of cytoplasmic large vacuoles upon actin disruption, and I determined that these large vacuoles are generated by macropinocytosis and endosomal pathway. Moreover, the vacuolization process is regulated by endophilinA2-, dynamin-dependent endocytosis, and requires class Ⅱ and Ⅲ PI3Ks, PIKfyve. Taken together, I characterize a new endocytosis induced by actin depolymerization in matrix-detached mammary epithelial cells, and suggest that actin disassembly may function as a rate-limiting factor to control lumen formation in mammary acini.