| Autor: |
Grochowska, Katarzyna M., Sperveslage, Marit, Raman, Rajeev, Failla, Antonio V., Głów, Dawid, Schulze, Christian, Laprell, Laura, Fehse, Boris, Kreutz, Michael R. |
| Zdroj: |
Cell Reports; Aug2023, Vol. 42 Issue 8, pN.PAG-N.PAG, 1p |
| Abstrakt: |
The complex morphology of neurons poses a challenge for proteostasis because the majority of lysosomal degradation machinery is present in the cell soma. In recent years, however, mature lysosomes were identified in dendrites, and a fraction of those appear to fuse with the plasma membrane and release their content to the extracellular space. Here, we report that dendritic lysosomes are heterogeneous in their composition and that only those containing lysosome-associated membrane protein (LAMP) 2A and 2B fuse with the membrane and exhibit activity-dependent motility. Exocytotic lysosomes dock in close proximity to GluN2B-containing N-methyl-D-aspartate-receptors (NMDAR) via an association of LAMP2B to the membrane-associated guanylate kinase family member SAP102/Dlg3. NMDAR-activation decreases lysosome motility and promotes membrane fusion. We find that chaperone-mediated autophagy is a supplier of content that is released to the extracellular space via lysosome exocytosis. This mechanism enables local disposal of aggregation-prone proteins like TDP-43 and huntingtin. [Display omitted] • LAMP1 and LAMP2B mark different dendritic vesicular populations • NMDAR activity induces fusion of LAMP2B-positive lysosomes with the plasma membrane • LAMP2B/LAMP2A lysosomes are competent for CMA • Lysosomal fusion leads to the extracellular release of CMA clients Grochowska et al. show that a subpopulation of dendritic lysosomes positive for lysosomal proteins LAMP2B and LAMP2A fuses with the plasma membrane upon activation of NMDA receptors. Activity-dependent fusion leads to the release of supersaturated, disease-relevant dendritic proteins huntingtin and TDP-43. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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