Journal article
Septins promote macropinosome maturation and traffic to the lysosome by facilitating membrane fusion
The Journal of cell biology, v 214(5), pp 517-527
29 Aug 2016
PMID: 27551056
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Macropinocytosis, the internalization of extracellular fluid and material by plasma membrane ruffles, is critical for antigen presentation, cell metabolism, and signaling. Macropinosomes mature through homotypic and heterotypic fusion with endosomes and ultimately merge with lysosomes. The molecular underpinnings of this clathrin-independent endocytic pathway are largely unknown. Here, we show that the filamentous septin GTPases associate preferentially with maturing macropinosomes in a phosphatidylinositol 3,5-bisphosphate-dependent manner and localize to their contact/fusion sites with macropinosomes/endosomes. Septin knockdown results in large clusters of docked macropinosomes, which persist longer and exhibit fewer fusion events. Septin depletion and overexpression down-regulates and enhances, respectively, the delivery of fluid-phase cargo to lysosomes, without affecting Rab5 and Rab7 recruitment to macropinosomes/endosomes. In vitro reconstitution assays show that fusion of macropinosomes/endosomes is abrogated by septin immunodepletion and function-blocking antibodies and is induced by recombinant septins in the absence of cytosol and polymerized actin. Thus, septins regulate fluid-phase cargo traffic to lysosomes by promoting macropinosome maturation and fusion with endosomes/lysosomes.
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Details
- Title
- Septins promote macropinosome maturation and traffic to the lysosome by facilitating membrane fusion
- Creators
- Lee Dolat - Department of Biology, Drexel University, Philadelphia, PA 19104Elias T Spiliotis - Department of Biology, Drexel University, Philadelphia, PA 19104 ets33@drexel.edu
- Publication Details
- The Journal of cell biology, v 214(5), pp 517-527
- Publisher
- United States
- Grant note
- F31 CA176910 / NCI NIH HHS R01 GM097664 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000382597700007
- Scopus ID
- 2-s2.0-84990872368
- Other Identifier
- 991014878294404721
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- Web of Science research areas
- Cell Biology