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Journal article
A septin GTPase scaffold of dynein-dynactin motors triggers retrograde lysosome transport
The Journal of cell biology, v 220(2)
01 Feb 2021
PMID: 33416861
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The metabolic and signaling functions of lysosomes depend on their intracellular positioning and trafficking, but the underlying mechanisms are little understood. Here, we have discovered a novel septin GTPase-based mechanism for retrograde lysosome transport. We found that septin 9 (SEPT9) associates with lysosomes, promoting the perinuclear localization of lysosomes in a Rab7-independent manner. SEPT9 targeting to mitochondria and peroxisomes is sufficient to recruit dynein and cause perinuclear clustering. We show that SEPT9 interacts with both dynein and dynactin through its GTPase domain and N-terminal extension, respectively. Strikingly, SEPT9 associates preferentially with the dynein intermediate chain (DIC) in its GDP-bound state, which favors dimerization and assembly into septin multimers. In response to oxidative cell stress induced by arsenite, SEPT9 localization to lysosomes is enhanced, promoting the perinuclear clustering of lysosomes. We posit that septins function as GDP-activated scaffolds for the cooperative assembly of dynein-dynactin, providing an alternative mechanism of retrograde lysosome transport at steady state and during cellular adaptation to stress.
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Details
- Title
- A septin GTPase scaffold of dynein-dynactin motors triggers retrograde lysosome transport
- Creators
- Ilona A. Kesisova - Drexel UniversityBenjamin P. Robinson - Department of Biology Drexel University Philadelphia PAElias T. Spiliotis - Drexel University
- Publication Details
- The Journal of cell biology, v 220(2)
- Publisher
- Rockefeller Univ Press
- Number of pages
- 23
- Grant note
- RO1 GM097664; R35 GM136337 / National Institutes of Health/National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000617417000001
- Scopus ID
- 2-s2.0-85099708761
- Other Identifier
- 991019168904204721
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- Web of Science research areas
- Cell Biology