PT  - JOURNAL ARTICLE
AU  - Meagan M. Postema
AU  - Nathan E. Grega-Larson
AU  - Leslie M. Meenderink
AU  - Matthew J. Tyska
TI  - PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli
AID  - 10.1101/686816
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 686816
4099  - http://biorxiv.org/content/early/2019/06/28/686816.short
4100  - http://biorxiv.org/content/early/2019/06/28/686816.full
AB  - Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule functions in controlling microvillar morphology. PACSIN2 KO enterocytes exhibit reduced numbers of microvilli and defects in microvillar ultrastructure, with membranes lifting away from rootlets of core bundles. Dynamin2, a PACSIN2 binding partner, and other endocytic factors were also lost from their normal localization near microvillar rootlets. To determine if loss of endocytic machinery could explain defects in microvillar morphology, we examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission fails, tubules are pulled into the cytoplasm and this, in turn, leads to a membrane lifting phenomenon reminiscent of that observed in PACSIN2 KO brush borders. These findings lead to a new model where inward forces generated by endocytic machinery on the plasma membrane control the membrane wrapping of cell surface protrusions.Highlight for TOC Apical microvilli increase the functional surface area of transporting epithelia. Here we report that the F-BAR domain-containing protein PACSIN2, through its ability to promote apical endocytosis, plays a critical role in controlling the morphology of intestinal brush border microvilli.