David P Corey — Page 2

PubMed2002

An inner ear gene expression database.

Microarray technology has provided an unprecedented opportunity to study gene expression profiles at a whole-genome level. As a first step toward a comprehensive understanding of inner ear gene expression, mouse cochleas were examined at two developmental stages (P2 and P32) using GeneChip oligonucleotide arrays. A large number of genes and ESTs (> 10,000) were found to be expressed in the cochlea. Expression profiles derived from duplicate samples at the same developmental stages showed general agreement and indicated the reproducibility of the assay. The expression of many known hair-cell genes was detected in the whole-cochlea samples, demonstrating the relatively high sensitivity of the assay. Genes highly expressed only at P2 or P32 were also identified and their expression patterns correlate with their functions in the cochlea. A web-based database with external links was set up for public access, which should facilitate the discovery of genes important in the development and function of the inner ear and should aid the identification of additional deafness genes.

Animals↗

PubMed2001

The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons.

Members of the BNaC/ASIC family of ion channels have been implicated in mechanotransduction and nociception mediated by dorsal root ganglion (DRG) neurons. These ion channels are also expressed in the CNS. We identified the PDZ domain protein PICK1 as an interactor of BNaC1(ASIC2) in a yeast two-hybrid screen. We show by two-hybrid assays, glutathione S-transferase pull-down assays, and coimmunoprecipitations that the BNaC1-PICK1 interaction is specific, and that coexpression of both proteins leads to their clustering in intracellular compartments. The interaction between BNaC1 and PICK1 requires the PDZ domain of PICK1 and the last four amino acids of BNaC1. BNaC1 is similar to two other BNaC/ASIC family members, BNaC2 (ASIC1) and ASIC4, at its extreme C terminus, and we show that PICK1 also interacts with BNaC2. We found that PICK1, like BNaC1 and BNaC2, is expressed by DRG neurons and, like the BNaC1alpha isoform, is present at their peripheral mechanosensory endings. Both PICK1 and BNaC1alpha are also coexpressed by some pyramidal neurons of the cortex, by pyramidal neurons of the CA3 region of hippocampus, and by cerebellar Purkinje neurons, localizing to their dendrites and cell bodies. Therefore, PICK1 interacts with BNaC/ASIC channels and may regulate their subcellular distribution or function in both peripheral and central neurons.

Acid Sensing Ion Channels↗