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Los genes clag3 del parásito de la malaria determinan la absorción de nutrientes mediada por el canal por parte de
Wang Nguitragool1, Abdullah A B Bokhari, Ajay D Pillai
1The Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Cell
|May 31, 2011
Resumen
Los investigadores identificaron la base molecular del canal aniónico de superficie plasmodial (PSAC), un transportador de nutrientes clave en los parásitos de la malaria. Este descubrimiento revela un nuevo objetivo para el desarrollo de fármacos antipalúdicos.
Área de la Ciencia:
- Parasitología Parasitología.
- Biología Molecular Biología Molecular
- Descubrimiento de Drogas Descubrimiento de Drogas
Sus antecedentes:
- El desarrollo del parásito de la malaria en los glóbulos rojos requiere la absorción de nutrientes a través de la membrana celular del huésped.
- El canal aniónico de superficie plasmodial (PSAC) facilita este transporte y es un objetivo antimalarial validado.
- La identidad molecular precisa y la función de los PSAC han permanecido elusivo.
Objetivo del estudio:
- Para identificar los genes parásitos responsables de la actividad del PSAC.
- Para dilucidar la base molecular del transporte de nutrientes a través de la membrana de los eritrocitos en Plasmodium falciparum.
- Validar el PSAC como un objetivo farmacológico mediante la caracterización de sus interacciones inhibidoras.
Principales métodos:
- Cribado de alto rendimiento para los inhibidores de la absorción de nutrientes.
- Mapeo genético utilizando una cruz de P. falciparum (Dd2 × HB3).
- Transfección de ADN y experimentos de selección in vitro.
- Análisis de la expresión del gen clag3 y la localización de proteínas.
Principales resultados:
- Se identificó un compuesto altamente específico para el PSAC de P. falciparum.
- La actividad de PSAC se mapeó a un solo locus en el cromosoma 3, que corresponde a dos genes clag3.
- Estos genes clag3 codifican una proteína de membrana integral que media la permeabilidad de los solutos.
- Se observó el cambio de expresión de los genes clag3.
Conclusiones:
- La familia de genes clag3 codifica el canal aniónico de superficie plasmodial (PSAC).
- El PSAC es esencial para la absorción de nutrientes durante el desarrollo intraeritrocitario del parásito de la malaria.
- La proteína codificada por clag3 representa un nuevo objetivo prometedor para el desarrollo de fármacos antipalúdicos.
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