caa a22 4500 606176624 CHVBK 20210128100748.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1705-1 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1705-1 A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane [Elektronische Daten] [Yuan Pan, Joseph Laird, David Yamaguchi, Sheila Baker] 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. The Author(s), 2014 Hyperpolarization gated channels nationallicence Photoreceptor nationallicence Neuron nationallicence Retina nationallicence Inner segment nationallicence HEK293 nationallicence Targeting nationallicence Localization nationallicence Di-arginine nationallicence RxR nationallicence HCN1 : Hyperpolarization and cyclic nucleotide-gated channel 1 nationallicence ER : Endoplasmic reticulum nationallicence TRIP8b : Tetratricopeptide repeat-containing Rab8b interacting protein nationallicence CNBD : Cyclic nucleotide-binding domain nationallicence KATP : ATP-sensitive potassium channels nationallicence Kir : Inward rectifier potassium channel nationallicence SUR : Sulphonylurea receptor nationallicence Pan Yuan Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut Laird Joseph Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut Yamaguchi David Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut Baker Sheila Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 833-843 1420-682X 72:4<833 2015 72 18 https://doi.org/10.1007/s00018-014-1705-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1705-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pan Yuan Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut NATIONALLICENCE 700 1- Laird Joseph Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut NATIONALLICENCE 700 1- Yamaguchi David Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut NATIONALLICENCE 700 1- Baker Sheila Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, 52242, Iowa City, IA, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 833-843 1420-682X 72:4<833 2015 72 18