Cellular vacuolization caused by overexpression of the PIKfyve-binding deficient Vac14L156R is rescued by starvation and inhibition of vacuolar-ATPase.
Biochim Biophys Acta Mol Cell Res
; 1864(5): 749-759, 2017 May.
Article
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| MEDLINE
| ID: mdl-28216340
ABSTRACT
Phosphoinositides (PI) and converting enzymes are crucial determinants of organelle identity and morphology. One important endolysosomal specific PI is PI(3,5)P2, generated by the PIKfyve kinase, which orchestrates in combination with Vac14 and Fig4. Dysfunction of this complex leads to large intracellular vacuoles in various cell types and is linked to neurological diseases. Here, we characterize the vacuolization phenotype caused by overexpression of the PIKfyve binding deficient mutant Vac14L156R in podocytes, which represent specialized cells of the kidney. Vacuolization of podocytes, which was associated with strong maturation defects in the endolysosomal system, could be completely rescued by starvation or treatment of cells with the v-ATPase inhibitor Bafilomycin A1. Moreover, we elucidated a strong and reversible de-vacuolization effect of the cholesterol export inhibitor U18666A, which was accompanied by increased basification of the lysosomal pH values. Taken together, our data give new hints to potential therapeutic targets in the treatment of disease linked to intracellular vacuolization.
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1
Bases de datos:
MEDLINE
Asunto principal:
Vacuolas
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Medio de Cultivo Libre de Suero
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Macrólidos
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Inhibidores Enzimáticos
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Podocitos
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Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Año:
2017
Tipo del documento:
Article