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The GTP- and Phospholipid-Binding Protein TTD14 Regulates Trafficking of the TRPL Ion Channel in Photoreceptor Cells


Protein trafficking in neurons occurs throughout the lifetime of a cell and includes the internalization and redistribution of plasma membrane proteins. Regulated protein trafficking controls the equipment of the plasma membrane with receptors and ion channels and thereby attenuates or enhances neuronal function. Defects in recycling of plasma membrane proteins can cause detrimental neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Down´s syndrome. In Drosophila photoreceptors, the TRPL ion channel, together with the TRP channel, mediates vision and light-dependently shuttles between an endomembrane storage compartment and the apical plasma membrane. Here, we report the identification of a mutation in the ttd14 gene that inhibits TRPL-trafficking in both directions and also results in photoreceptor degeneration. The TTD14 protein contains a region with weak homology to a PX-domain, which is also found in proteins that sort cargo in the endosome and enable protein recycling. We characterize TTD14 as a new regulator of photoreceptor maintenance and ion channel trafficking that binds to GTP and PtdIns(3)P, a phospholipid enriched in early endosomes.


Vyšlo v časopise: The GTP- and Phospholipid-Binding Protein TTD14 Regulates Trafficking of the TRPL Ion Channel in Photoreceptor Cells. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005578
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005578

Souhrn

Protein trafficking in neurons occurs throughout the lifetime of a cell and includes the internalization and redistribution of plasma membrane proteins. Regulated protein trafficking controls the equipment of the plasma membrane with receptors and ion channels and thereby attenuates or enhances neuronal function. Defects in recycling of plasma membrane proteins can cause detrimental neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Down´s syndrome. In Drosophila photoreceptors, the TRPL ion channel, together with the TRP channel, mediates vision and light-dependently shuttles between an endomembrane storage compartment and the apical plasma membrane. Here, we report the identification of a mutation in the ttd14 gene that inhibits TRPL-trafficking in both directions and also results in photoreceptor degeneration. The TTD14 protein contains a region with weak homology to a PX-domain, which is also found in proteins that sort cargo in the endosome and enable protein recycling. We characterize TTD14 as a new regulator of photoreceptor maintenance and ion channel trafficking that binds to GTP and PtdIns(3)P, a phospholipid enriched in early endosomes.


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