The GTP- and Phospholipid-Binding Protein TTD14 Regulates Trafficking of the TRPL Ion Channel in Drosophila Photoreceptor Cells
Autor: | Uwe Wolfrum, Alexander C. Cerny, Karla Baltner, Nathalie Maag, Krystina Schopf, Armin Huber, André Altendorfer, Elisabeth Sehn |
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Rok vydání: | 2015 |
Předmět: |
Rhodopsin
Cancer Research lcsh:QH426-470 Light GTP' Biology Eye 03 medical and health sciences Transient receptor potential channel Transient Receptor Potential Channels 0302 clinical medicine GTP-binding protein regulators GTP-Binding Proteins Genetics Animals Drosophila Proteins Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics Ion channel 030304 developmental biology 0303 health sciences Cell Membrane Membrane Proteins Darkness Rhabdomere Transport protein Cell biology lcsh:Genetics Protein Transport Drosophila melanogaster Membrane protein Mutation biology.protein Photoreceptor Cells Invertebrate 030217 neurology & neurosurgery Signal Transduction Research Article |
Zdroj: | PLoS Genetics PLoS Genetics, Vol 11, Iss 10, p e1005578 (2015) |
ISSN: | 1553-7404 |
Popis: | Recycling of signaling proteins is a common phenomenon in diverse signaling pathways. In photoreceptors of Drosophila, light absorption by rhodopsin triggers a phospholipase Cβ-mediated opening of the ion channels transient receptor potential (TRP) and TRP-like (TRPL) and generates the visual response. The signaling proteins are located in a plasma membrane compartment called rhabdomere. The major rhodopsin (Rh1) and TRP are predominantly localized in the rhabdomere in light and darkness. In contrast, TRPL translocates between the rhabdomeral plasma membrane in the dark and a storage compartment in the cell body in the light, from where it can be recycled to the plasma membrane upon subsequent dark adaptation. Here, we identified the gene mutated in trpl translocation defective 14 (ttd14), which is required for both TRPL internalization from the rhabdomere in the light and recycling of TRPL back to the rhabdomere in the dark. TTD14 is highly conserved in invertebrates and binds GTP in vitro. The ttd14 mutation alters a conserved proline residue (P75L) in the GTP-binding domain and abolishes binding to GTP. This indicates that GTP binding is essential for TTD14 function. TTD14 is a cytosolic protein and binds to PtdIns(3)P, a lipid enriched in early endosome membranes, and to phosphatidic acid. In contrast to TRPL, rhabdomeral localization of the membrane proteins Rh1 and TRP is not affected in the ttd14 P75L mutant. The ttd14 P75L mutation results in Rh1-independent photoreceptor degeneration and larval lethality suggesting that other processes are also affected by the ttd14 P75L mutation. In conclusion, TTD14 is a novel regulator of TRPL trafficking, involved in internalization and subsequent sorting of TRPL into the recycling pathway that enables this ion channel to return to the plasma membrane. Author Summary 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. |
Databáze: | OpenAIRE |
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