| Autor: |
Moy, S.S., Saintsing, A., Manuel de Villena, F.P., Koller, B.H., Nguyen, M., Mieczkowski, P., Armao, D., Church, R.J., Wheeler, M.L., Jania, L., Lorenzo, D.N., Snouwaert, J.N. |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| DOI: |
10.17615/px0z-4025 |
| Popis: |
Lysosomes play a critical role in maintenance of the integrity of neuronal function, and mutations in genes that contribute to lysosome formation, transport, and activity are associated with neurodegenerative disorders. Recently, the multisubunit complex, BLOC-one-related complex (BORC), has been shown to be involved in positioning lysosomes within the cytoplasm, although the consequences of altered BORC function in adult animals have not been established. We show that a spontaneous truncation mutation in the mouse Borcs7 gene, identified through whole-genome sequencing followed by genetic complementation, results in progressive axonal dystrophy with dramatic impairment of motor function. Furthermore, mice homozygous for deletion of the entire Borcs7 coding sequence die shortly after birth, and neurons cultured from these animals show impaired centrifugal transport of lysosomes. This identifies BORCS7 as a central factor in axonal transport of lysosomes and a possible target for improving disease-related disturbances in this important function. BORC is a multisubunit complex that regulates lysosomal positioning. Snouwaert et al. report that a truncation mutation in Borcs7, a subunit of this complex, results in reduced lysosomal transport, progressive axonal dystrophy, and impaired motor function in mice. Loss of Borcs7 causes juxtanuclear clustering of neuronal lysosomes and perinatal mortality. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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