Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/57895
Título: | Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures |
Autor(es): | Miranda, André Miguel Lopes Lasiecka, Zofia M. Xu, Yimeng Neufeld, Jessi Shahriar, Sanjid Simoes, Sabrina Chan, Robin B. Oliveira, Tiago Gil Small, Scott A. Di Paolo, Gilbert |
Palavras-chave: | Amyloid beta-Protein Precursor Animals Autophagy Biomarkers Cell Line, Tumor Class III Phosphatidylinositol 3-Kinases Exosomes HEK293 Cells Humans Lipids Lysophospholipids Lysosomes Mice, Inbred C57BL Mice, Knockout Monoglycerides Neurodegenerative Diseases Neurons Peptide Fragments Phosphatidylinositol Phosphates |
Data: | Jan-2018 |
Editora: | Nature Research |
Revista: | Nature Communications |
Citação: | Miranda, A. M., Lasiecka, Z. M., Xu, Y., Neufeld, J., et. al.(2018). Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. Nature communications, 9(1), 291 |
Resumo(s): | Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/57895 |
DOI: | 10.1038/s41467-017-02533-w |
ISSN: | 2041-1723 |
e-ISSN: | 2041-1723 |
Versão da editora: | https://www.nature.com/articles/s41467-017-02533-w |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
Miranda AM. Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.pdf | 3,59 MB | Adobe PDF | Ver/Abrir |