A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane

Yuan Pan; Joseph G Laird; David M Yamaguchi; Sheila A Baker

doi:10.1007/s00018-014-1705-1

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A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane

Journal article

Open access

Peer reviewed

A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane

Yuan Pan, Joseph G Laird, David M Yamaguchi and Sheila A Baker

Cellular and molecular life sciences : CMLS, Vol.72(4), pp.833-843

02/2015

DOI: 10.1007/s00018-014-1705-1

PMCID: PMC4309907

PMID: 25142030

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Abstract

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.

Amino Acid Sequence

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism

Humans

Secretory Pathway

Endoplasmic Reticulum - metabolism

Molecular Sequence Data

Animals, Genetically Modified - metabolism

Arginine - chemistry

Sequence Homology, Amino Acid

Sequence Alignment

Animals

Xenopus laevis - metabolism

Photoreceptor Cells - metabolism

HEK293 Cells

Cell Membrane - metabolism

Arginine - metabolism

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics

Amino Acid Substitution

Details

Title: Subtitle: A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane
Creators: Yuan Pan - Department of Biochemistry, Carver College of Medicine, University of Iowa, 51 Newton Road, Biochemistry, 4-712 BSB, Iowa City, IA, 52242, USA
Joseph G Laird
David M Yamaguchi
Sheila A Baker
Resource Type: Journal article
Publication Details: Cellular and molecular life sciences : CMLS, Vol.72(4), pp.833-843
DOI: 10.1007/s00018-014-1705-1
PMID: 25142030
PMCID: PMC4309907
NLM abbreviation: Cell Mol Life Sci
ISSN: 1420-682X
eISSN: 1420-9071
Publisher: Switzerland
Grant note: R01 EY020542 / NEI NIH HHS EY020542 / NEI NIH HHS
Language: English
Date published: 02/2015
Academic Unit: Iowa Neuroscience Institute; Biochemistry and Molecular Biology; University College Courses; Ophthalmology and Visual Sciences
Record Identifier: 9984024406702771

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