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

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  • Saeede Salehi
  • Abdolhossein Zare
  • Gianluca Prezza
  • Jakob Bader
  • Cornelius Schneider
  • Utz Fischer
  • Felix Meissner
  • Mann, Matthias
  • Michael Briese
  • Michael Sendtner

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.

OriginalsprogEngelsk
Artikelnummer4158
TidsskriftNature Communications
Vol/bind14
Antal sider19
ISSN2041-1723
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the Deutsche Forschungsgemeinschaft [BR4910/1-2 (SPP1738) and BR4910/2–2 (SPP1935) to M.B., SE697/4-2 (SPP1738) and SE697/5–2 (SPP1935) to M.S., Fi573/15-2 (SPP1935) and Fi573/20-1 to U.F.] and a Grant from the Schilling Stiftung im Stifterverband für die Deutsche Wissenschaft to M.S. This publication was supported by the Open Access Publication Fund of the University of Wuerzburg.

Publisher Copyright:
© 2023, The Author(s).

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