Macropinosome formation by tent pole ruffling in macrophages

Nicholas D. Condon, John M. Heddleston, Teng Leong Chew, Lin Luo, Peter S. McPherson, Maria S. Ioannou, Louis Hodgson, Jennifer L. Stow, Adam A. Wall

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Pathogen-mediated activation of macrophages arms innate immune responses that include enhanced surface ruffling and macropinocytosis for environmental sampling and receptor internalization and signaling. Activation of macrophages with bacterial lipopolysaccharide (LPS) generates prominent dorsal ruffles, which are precursors for macropinosomes. Very rapid, high-resolution imaging of live macrophages with lattice light sheet microscopy (LLSM) reveals new features and actions of dorsal ruffles, which redefine the process of macropinosome formation and closure. We offer a new model in which ruffles are erected and supported by F-actin tent poles that cross over and twist to constrict the forming macropinosomes. This process allows for formation of large macropinosomes induced by LPS. We further describe the enrichment of active Rab13 on tent pole ruffles and show that CRISPR deletion of Rab13 results in aberrant tent pole ruffles and blocks the formation of large LPS-induced macropinosomes. Based on the exquisite temporal and spatial resolution of LLSM, we can redefine the ruffling and macropinosome processes that underpin innate immune responses.

Original languageEnglish (US)
Pages (from-to)3873-3885
Number of pages13
JournalJournal of Cell Biology
Volume217
Issue number11
DOIs
StatePublished - Nov 1 2018

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Condon, N. D., Heddleston, J. M., Chew, T. L., Luo, L., McPherson, P. S., Ioannou, M. S., Hodgson, L., Stow, J. L., & Wall, A. A. (2018). Macropinosome formation by tent pole ruffling in macrophages. Journal of Cell Biology, 217(11), 3873-3885. https://doi.org/10.1083/jcb.201804137