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Journal article
Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes
The Journal of cell biology, v 217(9), pp 3141-3159
03 Sep 2018
PMCID: PMC6122995
PMID: 29907658
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D–positive lysosomes decreases steeply past the proximal segment. Unlike in fibroblasts, we found that the majority of dendritic Rab7 late endosomes (LEs) do not contain LAMP1 and that a large proportion of LAMP1 compartments do not contain CatB/D. Second, Rab7 activity is required to mobilize distal predegradative LEs for transport to the soma and terminal degradation. We conclude that the majority of dendritic LAMP1 endosomes are not degradative lysosomes and that terminal degradation of dendritic cargos such as Nsg1, Nsg2, and DNER requires Rab7-dependent transport in LEs to somatic lysosomes.
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Details
- Title
- Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes
- Creators
- Chan Choo Yap - University of VirginiaLaura Digilio - University of VirginiaLloyd P. McMahon - University of VirginiaA. Denise R. Garcia - Drexel UniversityBettina Winckler - University of Virginia
- Publication Details
- The Journal of cell biology, v 217(9), pp 3141-3159
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000443386900015
- Scopus ID
- 2-s2.0-85054071284
- Other Identifier
- 991019168701604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology