Rab31 and APPL2 enhance FcγR-mediated phagocytosis through PI3K/Akt signaling in macrophages

Yeo, Jeremy C., Wall, Adam A., Luo, Lin and Stow, Jennifer L. (2015) Rab31 and APPL2 enhance FcγR-mediated phagocytosis through PI3K/Akt signaling in macrophages. Molecular Biology of the Cell, 26 5: 952-965. doi:10.1091/mbc.E14-10-1457

Author Yeo, Jeremy C.
Wall, Adam A.
Luo, Lin
Stow, Jennifer L.
Title Rab31 and APPL2 enhance FcγR-mediated phagocytosis through PI3K/Akt signaling in macrophages
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1939-4586
Publication date 2015-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1091/mbc.E14-10-1457
Open Access Status DOI
Volume 26
Issue 5
Start page 952
End page 965
Total pages 14
Place of publication Bethesda, MD United States
Publisher American Society for Cell Biology
Collection year 2016
Language eng
Formatted abstract
Membrane remodeling in the early stages of phagocytosis enables the engulfment of particles or pathogens and receptor signaling to activate innate immune responses. Members of the Rab GTPase family and their disparate effectors are recruited sequentially to regulate steps throughout phagocytosis. Rab31 (Rab22b) is known for regulating post-Golgi trafficking, and here we show in macrophages that Rab31-GTP is additionally and specifically recruited to early-stage phagosomes. At phagocytic cups, Rab31 is first recruited during the phosphoinositide transition from PI(4,5)P2 to PI(3,4,5)P3, and it persists on PI(3)P-enriched phagosomes. During early phagocytosis, we find that Rab31 recruits the signaling adaptor APPL2. siRNA depletion of either Rab31 or APPL2 reduces FcγR-mediated phagocytosis. Mechanistically, this corresponds with a delay in the transition to PI(3,4,5)P3 and phagocytic cup closure. APPL2 depletion also reduced PI3K/Akt signaling and enhanced p38 signaling from FcγR. We thus conclude that Rab31/APPL2 is required for key roles in phagocytosis and prosurvival responses of macrophages. Of interest, in terms of localization and function, this Rab31/APPL2 complex is distinct from the Rab5/APPL1 complex, which is also involved in phagocytosis and signaling.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
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Created: Mon, 16 Mar 2015, 09:58:13 EST by Professor Jennifer Stow on behalf of Institute for Molecular Bioscience