@article{edb192d31bc04e88b20974b723447704,
title = "Macropinosome formation by tent pole ruffling in macrophages",
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.",
author = "Condon, {Nicholas D.} and Heddleston, {John M.} and Chew, {Teng Leong} and Lin Luo and McPherson, {Peter S.} and Ioannou, {Maria S.} and Louis Hodgson and Stow, {Jennifer L.} and Wall, {Adam A.}",
note = "Funding Information: Research funding was from the National Health and Medical Research Council of Australia (grants 1098710 and 1003021 to J.L. Stow), Australian Research Council (grants AAW LE170100206 and DP180101910 to J.L. Stow), and National Institutes of Health (grant CA205262 to L. Hodgson). PhD scholarship funding (N.D. Condon) was from the Australian government and Yulgilbar Alzheimer Research Program. P.S. McPherson is a James McGill Professor and is supported by a Foundation Grant from the Canadian Institutes of Health Research. L. Hodgson is an Irma T. Hirschl Career Scientist. Funding Information: Research funding was from the National Health and Medical Research Council of Australia (grants 1098710 and 1003021 to J.L. Stow), Australian Research Council (grants AAW LE170100206 and DP180101910 to J.L. Stow), and National Institutes of Health (grant CA205262 to L. Hodgson). PhD scholarship funding (N.D. Condon) was from the Australian government and Yulgilbar Alzheimer Research Program. P.S. McPherson is a James McGill Professor and is supported by a Foundation Grant from the Canadian Institutes of Health Research. L. Hodgson is an Irma T. Hirschl Career Scientist. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2018 Condon et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).",
year = "2018",
month = nov,
day = "1",
doi = "10.1083/jcb.201804137",
language = "English (US)",
volume = "217",
pages = "3873--3885",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "11",
}