RESUMO
The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells.
Assuntos
Ativação do Canal Iônico , Pressão Osmótica , Receptores de Droga/metabolismo , Sequência de Aminoácidos , Animais , Repetição de Anquirina/genética , Repetição de Anquirina/fisiologia , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Células CHO , Sinalização do Cálcio , Cátions/metabolismo , Galinhas/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Clonagem Molecular , Cricetinae , Eletrofisiologia , Perfilação da Expressão Gênica , Células Ciliadas Auditivas Internas/química , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Internas/fisiologia , Humanos , Soluções Hipotônicas , Hibridização In Situ , Células de Merkel/química , Células de Merkel/metabolismo , Camundongos , Dados de Sequência Molecular , Neurônios Aferentes/química , Neurônios Aferentes/metabolismo , Neurônios Aferentes/fisiologia , Concentração Osmolar , Filogenia , RNA Mensageiro/análise , RNA Mensageiro/genética , Mapeamento de Híbridos Radioativos , Ratos , Receptores de Droga/química , Receptores de Droga/genética , Alinhamento de SequênciaRESUMO
We have identified a novel cochlear gene, designated OTOR, from a comparative sequence analysis of over 4000 clones from a human fetal cochlear cDNA library. Northern blot analysis of human and chicken organs shows strong OTOR expression only in the cochlea; very low levels are detected in the chicken eye and spinal cord. Otor and Col2A1 are coexpressed in the cartilaginous plates of the neural and abneural limbs of the chicken cochlea, structures analogous to the mammalian spiral limbus, osseous spiral lamina, and spiral ligament, and not in any other tissues in head and body sections. The human OTOR gene localizes to chromosome 20 in bands p11.23-p12.1 and more precisely to STS marker WI-16380. We have isolated cDNAs orthologous to human OTOR in the mouse, chicken, and bullfrog. The encoded protein, designated otoraplin, has a predicted secretion signal peptide sequence and shows a high degree of cross-species conservation. Otoraplin is homologous to the protein encoded by CDRAP/MIA (cartilage-derived retinoic acid sensitive protein/melanoma inhibitory activity), which is expressed predominantly by chondrocytes, functions in cartilage development and maintenance, and has growth-inhibitory activity in melanoma cell lines.