Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins

Putz, Ulrich, Howitt, Jason, Lackovic, Jenny, Foot, Natalie, Kumar, Sharad, Silke, John and Tan, Seong-Seng (2008) Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. Journal of Biological Chemistry, 283 47: 32621-32627. doi:10.1074/jbc.M804120200

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Author Putz, Ulrich
Howitt, Jason
Lackovic, Jenny
Foot, Natalie
Kumar, Sharad
Silke, John
Tan, Seong-Seng
Title Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2008-11-21
Year available 2008
Sub-type Article (original research)
DOI 10.1074/jbc.M804120200
Open Access Status File (Publisher version)
Volume 283
Issue 47
Start page 32621
End page 32627
Total pages 7
Place of publication Rockville, MD United States
Publisher American Society for Biochemistry and Molecular Biology, Inc.
Collection year 2008
Language eng
Subject 1303 Specialist Studies in Education
1307 Cell Biology
1312 Molecular Biology
Abstract The ability to remove unwanted proteins is an important cellular feature. Classically, this involves the enzymatic addition of ubiquitin moieties followed by degradation in the proteasome. Nedd4 proteins are ubiquitin ligases important not only for protein degradation, but also for protein trafficking. Nedd4 proteins can bind to target proteins either by themselves or through adaptor protein Ndfip1 (Nedd4 family-interacting protein 1). An alternative mechanism for protein removal and trafficking is provided by exosomes, which are small vesicles (50-90-nm diameter) originating from late endosomes and multivesicular bodies (MVBs). Exosomes provide a rapid means of shedding obsolete proteins and also for cell to cell communication. In the present work, we show that Ndfip1 is detectable in exosomes secreted from transfected cells and also from primary neurons. Compared with control, Ndfip1 increases exosome secretion from transfected cells. Furthermore, while Nedd4, Nedd4-2, and Itch are normally absent from exosomes, expression of Ndfip1 results in recruitment of all three Nedd4 proteins into exosomes. Together, these results suggest that Ndfip1 is important for protein trafficking via exosomes, and provides a mechanism for cargoing passenger proteins such as Nedd4 family proteins. Given the positive roles of Ndfip1/Nedd4 in improving neuronal survival during brain injury, it is possible that exosome secretion provides a novel route for rapid sequestration and removal of proteins during stress.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 56 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 27 Oct 2014, 17:18:46 EST by Sylvie Pichelin on behalf of Queensland Brain Institute