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A role for SNX5 in the regulation of macropinocytosis

Lim, Jet Phey, Wang, Jack TH, Kerr, Markus C, Teasdale, Rohan D and Gleeson, Paul A 2008, A role for SNX5 in the regulation of macropinocytosis, BMC Molecular and Cell Biology, vol. 9, pp. 1-12, doi: 10.1186/1471-2121-9-58.

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Title A role for SNX5 in the regulation of macropinocytosis
Author(s) Lim, Jet PheyORCID iD for Lim, Jet Phey orcid.org/0000-0003-1357-4751
Wang, Jack TH
Kerr, Markus C
Teasdale, Rohan D
Gleeson, Paul A
Journal name BMC Molecular and Cell Biology
Volume number 9
Article ID 58
Start page 1
End page 12
Total pages 12
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2008
ISSN 1471-2121
Summary BackgroundThe mechanisms and components that regulate macropinocytosis are poorly understood. Here we have investigated the role of sorting nexin 5 (SNX5) in the regulation of macropinocytic activity.ResultsSNX5 is abundantly expressed in macrophages, cells very active in macropinocytosis, and is recruited onto newly-formed macropinosomes. LPS treatment of bone marrow-derived macrophages resulted in a 2.5 fold decrease in macropinosome formation that correlates with a reduction in the levels of SNX5. To investigate the relationship between SNX5 levels and macropinocytic activity we examined the formation of macropinosomes in HEK-FlpIn cells stably expressing GFP-SNX5. Constitutive macropinocytosis was increased ~2 fold in HEK-GFP-SNX5 cells compared with parental HEK-FlpIn cells. Furthermore, EGF stimulation resulted in a significant increase in macropinocytosis and there was also a 2.0 fold increase in the generation of macropinosomes in HEK-GFP-SNX5 cells compared with parental HEK-FlpIn cells. SNX5, which interacts specifically with PtdIns(3)P and PtdIns(3,4)P2 through its PX domain, was recruited to regions on the plasma membrane containing EGF receptor or positive for PtdIns(3,4)P2 as detected with the PH domain of TAPP1. Treatment with AG1478, an EGF receptor specific tyrosine kinase inhibitor, prevented the recruitment of SNX5 to the cytosolic face of the plasma membrane and inhibited the formation of macropinosomes in response to EGF treatment.ConclusionBased on these data, we propose that SNX5 requires the generation of phosphoinositides for recruitment to the plasma membrane and, moreover, influences the level of macropinocytic activity.
Language eng
DOI 10.1186/1471-2121-9-58
Indigenous content off
Field of Research 0601 Biochemistry and Cell Biology
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, Lim et al
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30131060

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.