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

Salehi, S., Zare, A., Prezza, G., Bader, J. M., Schneider, C., Fischer, U., et al. (2023). Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr. Nature Communications, 14(1): 4158. doi:10.1038/s41467-023-39787-6.

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 Urheber:
Salehi, Saeede, Autor
Zare, Abdolhossein, Autor
Prezza, Gianluca, Autor
Bader, Jakob Maximilian1, Autor           
Schneider, Cornelius, Autor
Fischer, Utz, Autor
Meissner, Felix1, 2, Autor           
Mann, Matthias1, Autor           
Briese, Michael, Autor
Sendtner, Michael, Autor
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Schlagwörter: INITIATION-FACTOR 5A; SYNAPTIC PLASTICITY; PROTEIN-SYNTHESIS; SPINAL-CORD; IDENTIFICATION; HYPUSINE; VISUALIZATION; MUTATIONS; PLATFORM; BINDINGScience & Technology - Other Topics;
 Zusammenfassung: 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.
The neuronal RNA-binding protein Ptbp2 is known to regulate neuronal differentiation by modulating alternative splicing. Here, the authors reveal an additional role of cytosolic Ptbp2, which regulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein hnRNP R.

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Sprache(n): eng - English
 Datum: 2023-07-122023
 Publikationsstatus: Erschienen
 Seiten: 19
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 001029450400019
DOI: 10.1038/s41467-023-39787-6
 Art des Abschluß: -

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Titel: Nature Communications
  Kurztitel : Nat. Commun.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: London : Nature Publishing Group
Seiten: - Band / Heft: 14 (1) Artikelnummer: 4158 Start- / Endseite: - Identifikator: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723