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PMID: 9405696 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels.

Santoro B, Grant SG, Bartsch D, Kandel ER

Abstract

We have isolated a novel cDNA, that appears to represent a new class of ion channels, by using the yeast two-hybrid system and the SH3 domain of the neural form of Src (N-src) as a bait. The encoded polypeptide, BCNG-1, is distantly related to cyclic nucleotide-gated channels and the voltage-gated channels, Eag and H-erg. BCNG-1 is expressed exclusively in the brain, as a glycosylated protein of approximately 132 kDa. Immunohistochemical analysis indicates that BCNG-1 is preferentially expressed in specific subsets of neurons in the neocortex, hippocampus, and cerebellum, in particular pyramidal neurons and basket cells. Within individual neurons, the BCNG-1 protein is localized to either the dendrites or the axon terminals depending on the cell type. Southern blot analysis shows that several other BCNG-related sequences are present in the mouse genome, indicating the emergence of an entire subfamily of ion channel coding genes. These findings suggest the existence of a new type of ion channel, which is potentially able to modulate membrane excitability in the brain and could respond to regulation by cyclic nucleotides.

MeSH Terms
Amino Acid Sequence Animals Brain/metabolism Cloning, Molecular Cyclic Nucleotide-Gated Cation Channels Ether-A-Go-Go Potassium Channels Genes, src Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channel Gating Ion Channels/genetics,isolation & purification Mice Molecular Sequence Data Nerve Tissue Proteins/genetics,isolation & purification Nucleotides, Cyclic Organ Specificity Potassium Channels/genetics Sequence Alignment src Homology Domains/genetics
Chemicals
Cyclic Nucleotide-Gated Cation Channels Ether-A-Go-Go Potassium Channels Hcn1 protein, mouse Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Ion Channels Nerve Tissue Proteins Nucleotides, Cyclic Potassium Channels
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Santoro B
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, and Howard Hughes Medical Institute, 722 West 168th Street, New York, NY 10032, USA.
Grant S G
Bartsch D
Kandel E R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1997-12-23
Pages
14815-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25120
Subset
IM
Databases
GENBANK
AF028737, AF064873, AF064874, AF064875, AF064876, AF064877
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