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Sorting nexin 5 selectively regulates dorsal-ruffle-mediated macropinocytosis in primary macrophages

Lim, Jet Phey, Gosavi, Prajakta, Mintern, Justine D., Ross, Ellen M. and Gleeson, Paul A. 2015, Sorting nexin 5 selectively regulates dorsal-ruffle-mediated macropinocytosis in primary macrophages, Journal of Cell Science, vol. 128, no. 23, pp. 4407-4419, doi: 10.1242/jcs.174359.

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Title Sorting nexin 5 selectively regulates dorsal-ruffle-mediated macropinocytosis in primary macrophages
Author(s) Lim, Jet PheyORCID iD for Lim, Jet Phey orcid.org/0000-0003-1357-4751
Gosavi, Prajakta
Mintern, Justine D.
Ross, Ellen M.
Gleeson, Paul A.
Journal name Journal of Cell Science
Volume number 128
Issue number 23
Start page 4407
End page 4419
Total pages 13
Publisher The Company of Biologists
Place of publication Cambridge, Eng.
Publication date 2015-12-01
ISSN 0021-9533
1477-9137
Keyword(s) macropinocytosis
sorting nexin
SNX5
dorsal ruffle
endocytosis
antigen processing
Summary The regulation of macropinocytosis, a specialised endocytosis pathway, is important for immune cell function. However, it is not known whether the biogenesis of macropinosomes involves one or more distinct pathways. We previously identified sorting nexin 5 (SNX5) as a regulator of macropinocytosis in macrophages. Here, we show that bone-marrow-derived macrophages from SNX5-knockout mice had a 60–70% reduction in macropinocytic uptake of dextran or ovalbumin, whereas phagocytosis and retrograde transport from the plasma membrane to the Golgi was unaffected. In contrast, deficiency of SNX5 had no effect on macropinocytosis or antigen presentation by dendritic cells. Activation of macrophages with CSF-1 resulted in a localisation of SNX5 to actin-rich ruffles in a manner dependent on receptor tyrosine kinases. SNX5-deficient macrophages showed a dramatic reduction in ruffling on the dorsal surface following CSF-1 receptor activation, whereas peripheral ruffling and cell migration were unaffected. We demonstrate that SNX5 is acting upstream of actin polymerisation following CSF-1 receptor activation. Overall, our findings reveal the important contribution of dorsal ruffing to receptor-activated macropinocytosis in primary macrophages and show that SNX5 selectively regulates macropinosomes derived from the dorsal ruffles.
Language eng
DOI 10.1242/jcs.174359
Indigenous content off
Field of Research 06 Biological Sciences
11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, The Company of Biologists
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30131056

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.