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DOI: 10.14670/HH-11-862
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Título: | Targeting exogenous β-Defensin to the endolysosomal compartment via a vehicle guided system |
Fecha de publicación: | 2017 |
Editorial: | Universidad de Murcia. Departamento de Biología Celular e Histología |
Cita bibliográfica: | Histology and Histopathology, Vol.32, nº10, (2017) |
ISSN: | 1699-5848 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | Antimicrobial proteins β-Defensin Prosaposin Sortilin Endosomes Lysosomes Lysosomal trafficking |
Resumen: | A number of pathogens for which there are no effective treatments infect the cells via endocytosis. Once in the endosomes, the pathogens complete their life cycle by overriding normal lysosomal functions. Recently, our laboratory identified the lysosomal targeting signal of prosaposin, which is recognized by the sorting receptor “sortilin”. Based on this evidence, we tested whether the antimicrobial peptide β-Defensin linked to the targeting sequence of prosaposin (βDPSAP) could be redirected from its secretory pathway to the endolysosomal compartment. To this effect, βDPSAP was transfected into COS-7 cells. The sub-cellular distribution of βD-PSAP was analyzed by confocal microscopy and differential centrifugation. Confocal microscopy demonstrated that βD-PSAP overlaid with the lysosomal marker LAMP1, indicating that the construct reached endosomes and lysosomes. Differential centrifugation also showed that βD-PSAP was in the lysosomal fractions. In addition, our binding inhibition assay demonstrated that βD-PSAP bound specifically to sortilin. Similarly, the delivery of βDPSAP was abolished after overexpressing a truncated sortilin. These results indicate that the prosaposin Cterminus and D/C-domain (prosaposin targeting sequence) was an effective “guidance system” to redirect βD-PSAP to the endolysosomal compartment. In the future, this and other fusion proteins with antimicrobial properties will be assembled to our “biotic vehicle” to target pathogens growing within these compartments. |
Autor/es principal/es: | Carvelli, Lorena Libin, Yuan Esfandnia, Sherry Zhang, Yan Presley, John F. Morales, Carlos R. |
URI: | http://hdl.handle.net/10201/117743 |
DOI: | DOI: 10.14670/HH-11-862 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 11 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Aparece en las colecciones: | Vol.32,nº10 (2017) |
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Fichero | Descripción | Tamaño | Formato | |
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Carvelli-32-1017-1027-2017.pdf | 3,87 MB | Adobe PDF | Visualizar/Abrir |
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