Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival.

Autor:	Fukuda Y; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Pazyra-Murphy MF; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Silagi ES; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Tasdemir-Yilmaz OE; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Li Y; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Rose L; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Yeoh ZC; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Vangos NE; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Geffken EA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA., Seo HS; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA., Adelmant G; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA.; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA.; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Bird GH; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA., Walensky LD; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA., Marto JA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA.; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA.; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Dhe-Paganon S; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA., Segal RA; Department of Neurobiology, Harvard Medical School, Boston, MA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2021 Jan 04; Vol. 220 (1).
DOI:	10.1083/jcb.202005051
Abstrakt:	Complex neural circuitry requires stable connections formed by lengthy axons. To maintain these functional circuits, fast transport delivers RNAs to distal axons where they undergo local translation. However, the mechanism that enables long-distance transport of RNA granules is not yet understood. Here, we demonstrate that a complex containing RNA and the RNA-binding protein (RBP) SFPQ interacts selectively with a tetrameric kinesin containing the adaptor KLC1 and the motor KIF5A. We show that the binding of SFPQ to the KIF5A/KLC1 motor complex is required for axon survival and is impacted by KIF5A mutations that cause Charcot-Marie Tooth (CMT) disease. Moreover, therapeutic approaches that bypass the need for local translation of SFPQ-bound proteins prevent axon degeneration in CMT models. Collectively, these observations indicate that KIF5A-mediated SFPQ-RNA granule transport may be a key function disrupted in KIF5A-linked neurologic diseases and that replacing axonally translated proteins serves as a therapeutic approach to axonal degenerative disorders. (© 2020 Fukuda et al.)
Databáze:	MEDLINE
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