RESUMO
Endocytosed cholesterol must be transferred from the environment (e.g., low-density lipoproteins) via the lysosomal system to the rest of the cell. In Niemann-Pick type C disease, this process fails. In a recent issue of Cell, Kwon et al. (2009) suggest how this transpires mechanistically by crystallizing a domain of a protein defective in this syndrome.
Assuntos
Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Glicoproteínas de Membrana/metabolismo , Transporte Biológico , Proteínas de Transporte/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Glicoproteínas de Membrana/química , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C/metabolismo , Ligação Proteica , Estrutura Terciária de ProteínaAssuntos
Lipídeos/fisiologia , Doenças de Niemann-Pick/metabolismo , Esteróis/metabolismo , 2-Hidroxipropil-beta-Ciclodextrina , Animais , Transporte Biológico , Colesterol/metabolismo , Excipientes/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lipídeos/química , Lisossomos/metabolismo , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Mutação , Proteína C1 de Niemann-Pick , Proteínas/metabolismo , beta-Ciclodextrinas/farmacologiaRESUMO
Understanding the molecular basis of Niemann-Pick C (NP-C) disease took decades of struggle. Here I describe our early efforts to unravel the complex lipid storage found in NP-C tissues, and how the mouse model for NP-C pointed us in the right direction. Our success in cloning the NP-C1 gene in 1997 can be attributed to collaboration between an international body of scientists and families coping with NP-C disease. The next challenge is to delineate the biological function of the NP-C1 protein.
