Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr.

Autor: Salehi S; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany., Zare A; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany., Prezza G; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany.; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Wuerzburg, Germany., Bader J; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Schneider C; Department of Biochemistry, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany., Fischer U; Department of Biochemistry, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg, Germany., Meissner F; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany.; Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany., Mann M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.; NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Briese M; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany. Briese_M@ukw.de., Sendtner M; Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany. Sendtner_M@ukw.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 12; Vol. 14 (1), pp. 4158. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1038/s41467-023-39787-6
Abstrakt: The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3' UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: