A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane
| Autor: | Joseph G. Laird, David M. Yamaguchi, Yuan Pan, Sheila A. Baker |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
HEK293
Molecular Sequence Data Mutant Xenopus Biology Arginine Endoplasmic Reticulum Retina Animals Genetically Modified Cell membrane Xenopus laevis Cellular and Molecular Neuroscience Inner segment Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Humans Photoreceptor Cells Amino Acid Sequence Hyperpolarization gated channels Molecular Biology Secretory pathway Pharmacology Targeting Photoreceptor Secretory Pathway Sequence Homology Amino Acid Endoplasmic reticulum Cell Membrane HEK 293 cells RxR Wild type ER retention Cell Biology Neuron biology.organism_classification Cell biology HEK293 Cells medicine.anatomical_structure Amino Acid Substitution Biochemistry Localization Di-arginine Molecular Medicine Sequence Alignment Research Article |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-014-1705-1 |
| Popis: | Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels carry Ih, which contributes to neuronal excitability and signal transmission in the nervous system. Controlling the trafficking of HCN1 is an important aspect of its regulation, yet the details of this process are poorly understood. Here, we investigated how the C-terminus of HCN1 regulates trafficking by testing for its ability to redirect the localization of a non-targeted reporter in transgenic Xenopus laevis photoreceptors. We found that HCN1 contains an ER localization signal and through a series of deletion constructs, identified the responsible di-arginine ER retention signal. This signal is located in the intrinsically disordered region of the C-terminus of HCN1. To test the function of the ER retention signal in intact channels, we expressed wild type and mutant HCN1 in HEK293 cells and found this signal negatively regulates surface expression of HCN1. In summary, we report a new mode of regulating HCN1 trafficking: through the use of a di-arginine ER retention signal that monitors processing of the channel in the early secretory pathway. Electronic supplementary material The online version of this article (doi:10.1007/s00018-014-1705-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink