Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr
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Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr. / Salehi, Saeede; Zare, Abdolhossein; Prezza, Gianluca; Bader, Jakob; Schneider, Cornelius; Fischer, Utz; Meissner, Felix; Mann, Matthias; Briese, Michael; Sendtner, Michael.
In: Nature Communications, Vol. 14, 4158, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr
AU - Salehi, Saeede
AU - Zare, Abdolhossein
AU - Prezza, Gianluca
AU - Bader, Jakob
AU - Schneider, Cornelius
AU - Fischer, Utz
AU - Meissner, Felix
AU - Mann, Matthias
AU - Briese, Michael
AU - Sendtner, Michael
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-39787-6
DO - 10.1038/s41467-023-39787-6
M3 - Journal article
C2 - 37438340
AN - SCOPUS:85164540580
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4158
ER -
ID: 362699599