A voltage-gated proton-selective channel lacking the pore domain
I Scott Ramsey1, Magdalene M Moran, Jayhong A Chong
1Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|March 24, 2006
Summary
Researchers identified a novel mammalian voltage-gated proton channel (H(v)1) that lacks a pore domain but is crucial for immune cell function. This discovery advances understanding of proton transport and innate immunity.
Area of Science:
- Molecular Biology
- Cell Physiology
- Immunology
Background:
- Voltage-gated ion channels, crucial for cellular function, possess voltage-sensing domains (VSDs) that regulate gating.
- While VSDs are typically linked to ion channel pores, some VSD proteins, like Ci-VSP, function independently of channels.
- The existence and function of mammalian voltage-gated proton channels remained largely uncharacterized.
Purpose of the Study:
- To identify and characterize a novel mammalian voltage-gated proton channel.
- To elucidate the functional properties and regulatory mechanisms of this newly identified channel.
- To determine the role of this channel in immune responses.
Main Methods:
- Expression and electrophysiological analysis of a mammalian VSD protein, H(v)1.
- Site-directed mutagenesis to identify key residues involved in gating and inhibition.
- Investigation of H(v)1 expression in immune tissues and its role in phagocytic leukocytes.
Main Results:
- A mammalian VSD protein, H(v)1, was identified as a functional voltage-gated proton channel, independent of a discernible pore domain.
- H(v)1 currents are activated by depolarization, are proton-selective, and are inhibited by Zn2+ via specific histidine residues.
- H(v)1 is expressed in immune cells and mediates proton conductance (G(vH+)) essential for the oxidative burst in phagocytes.
Conclusions:
- H(v)1 represents the first identified mammalian voltage-gated proton channel, expanding the known functions of VSD proteins.
- The study establishes H(v)1 as a critical component of the innate immune system, particularly in microbial killing.
- H(v)1 is the founding member of a new family of mammalian VSD proteins with diverse physiological roles.
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