Project 5:
Exosome transport of Ndfip1 – a pathway for rapid cellular trafficking
The ability to remove unwanted proteins involves ubiquitination followed by degradation of the unwanted proteins in the proteasome. 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). Cells undergoing stress conditions show increased exosome release. Ndfip1 is an important protein for exosome transport of proteins that bind to Ndfip1 (Putz et al., 2008). In this project, we will investigate how this pathway may be linked to neuron stress following injury. We will study the molecular pathways controlling exosome release in stress, and ultimately how this pathway may be harnessed for improving neuron survival.
Publications
Sang, Q., Kim, M., Kumar, S., Bye, N., Morganti-Kossman, M.C., Gunnersen, J., Fuller, S., Howitt, J., Hyde, L., Beissbarth, T., Scott, H.S., Silke,, J. and Tan, S-S (2006)
Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal survival following acute cortical brain injury.
J. Neurosci. 26:7234-7244
Putz, U.,, Howitt, J., Lackovic, J., Foot, N., Kumar, S., Silke, J. and Tan, S-S (2008)
Nedd4-family interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4-family proteins.
J. Biol. Chem 283:32621-32627
Howitt, J., Putz, U., Lackovic, J., Doan, A., Dorstyn, L., Cheng, H., Yang, B., Chan-Ling, T., Silke, J., Kumar, S. and Tan, S-S (2009)
Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons.
Proc. Natl. Acad. Sci. USA 106:15489-15494
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