Assuntos
Regulação da Expressão Gênica , Genes de Protozoários , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Amanitinas/farmacologia , Animais , Células Cultivadas , Células Epiteliais , Inativação Gênica , Humanos , Pulmão/citologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Regiões Promotoras Genéticas , Proteínas de Protozoários/genética , RNA de Protozoário/genética , RNA de Protozoário/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
The human malarial parasite Plasmodium falciparum exports proteins to destinations within its host erythrocyte, including cytosol, surface and membranous profiles of parasite origin termed Maurer's clefts. Although several of these exported proteins are determinants of pathology and virulence, the mechanisms and trafficking signals underpinning protein export are largely uncharacterized-particularly for exported transmembrane proteins. Here, we have investigated the signals mediating trafficking of STEVOR, a family of transmembrane proteins located at the Maurer's clefts and believed to play a role in antigenic variation. Our data show that, apart from a signal sequence, a minimum of two addition signals are required. This includes a host cell targeting signal for export to the host erythrocyte and a transmembrane domain for final sorting to Maurer's clefts. Biochemical studies indicate that STEVOR traverses the secretory pathway as an integral membrane protein. Our data suggest general principles for transport of transmembrane proteins to the Maurer's clefts and provide new insights into protein sorting and trafficking processes in P. falciparum.