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.
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.
Santoro
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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
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SG
Bartsch
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Kandel
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ER
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D054815:Cyclic Nucleotide-Gated Cation Channels; D051638:Ether-A-Go-Go Potassium Channels; D016391:Genes, src; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015640:Ion Channel Gating; D007473:Ion Channels / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification; D009712:Nucleotides, Cyclic; D009928:Organ Specificity; D015221:Potassium Channels / Q000235:genetics*; D016415:Sequence Alignment; D018909:src Homology Domains / Q000235:genetics*
D054815:Cyclic Nucleotide-Gated Cation Channels; D051638:Ether-A-Go-Go Potassium Channels; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D009712:Nucleotides, Cyclic; D015221:Potassium Channels