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Evolutionary conservation of Notch signaling inhibition by TMEM131L overexpression

Abstract : Human KIAA0922/TMEM131L encodes a transmembrane protein, TMEM131L, that regulates the canonical Wnt/b-catenin signaling pathway by eliciting the lysosome-dependent degradation of phosphorylated LRP6 co-receptor. Here, we use a heterospecific Drosophila transgenic model to examine the potential evolutionary conservation of TMEM131L function. Analysis of TMEM131L transgenic flies shows that TMEM131L interference with the Wnt pathway results primarily from a Notch-dependent decrease in Wingless production. Consistently, lentivirus-mediated overexpression of TMEM131L in human CD34 þ hematopoietic progenitor cells leads to decreased susceptibility to Notch1 ligation and defective commitment toward the T lineage. These results show that TMEM131L corresponds to an evolutionary conserved regulator of the Notch signaling pathway.
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https://hal.uvsq.fr/hal-02975504
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Submitted on : Thursday, October 22, 2020 - 5:18:33 PM
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Sebastien Szuplewski, Nesrine Maharzi, Elisabeth Nelson, Kutaiba Alhaj Hussen, Bernard Mignotte, et al.. Evolutionary conservation of Notch signaling inhibition by TMEM131L overexpression. Biochemical and Biophysical Research Communications, Elsevier, 2017, ⟨10.1016/j.bbrc.2017.03.123⟩. ⟨hal-02975504⟩

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