The Drosophila homolog of the human disease genes .. (Spict BMP Traffic)
The Drosophila homolog of the human disease genes SPG6 and ichthyin - its role in BMP and TGF-beta signaling
(Spict BMP Traffic)
Start date: Aug 15, 2008,
End date: Aug 14, 2010
Spichthyin (Spict) is the Drosophila homolog of the human disease genes SPG6 (mutated in some hereditary spastic paraplegias) and ichthyin (mutated in some ichthyoses). The host lab has recently assigned a cellular role to this protein family, by showing that Spict is an endosomal membrane protein that antagonises the BMP signaling pathway in neurons and S2 cells, causing internalisation of receptors from the cell surface to the endosome. The main goal of this project is to understand how Spict affects BMP signaling. Binding partners of Spict will be identified, and validated by biochemical and microscopic methods. Effects of manipulating binding partners, on localisation and trafficking of Spict and BMP receptors, will be tested. Trafficking pathways of Spict, BMP receptors and if possible of any novel binding partners, relative to other membrane-bound markers relevant to BMP signaling,, will be investigated, using both fixed and live preparations. Using these approaches we aim for a better understanding of the intracellular membrane trafficking pathways of BMP receptors. This will be important both for our basic biological knowledge of a pathway of wide important in development and neuronal function, and for understanding mechanisms of pathology that may be relevant to a range of motor neuron and axonal degenerative diseases.
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