Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human.

Tang, P.-C.; Um, S.; Mayfield, A. B.; Bracho, O. R.; Del Castillo, C.; Dinh, C. T.; Dykxhoorn, D. M.; Liu, X. Z.

doi:10.1101/2024.09.24.614711

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bioRxiv · 10.1101/2024.09.24.614711

Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human.

Tang, P.-C.·Um, S.·Mayfield, A. B.·Bracho, O. R.·Del Castillo, C.·Dinh, C. T.·Dykxhoorn, D. M.·Liu, X. Z.

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Abstract

NF2-Related Schwannomatosis (previously referred to as Neurofibromatosis Type 2, or NF2) is a genetic-associated disease resulting from mutations in the gene, NF2. NF2 encodes the merlin protein, which acts as a tumor suppressor. Bilateral vestibular schwannoma (VS) is a hallmark of NF2. Although the exactly molecular mechanism mediating NF2-driven schwannomatosis remain unclear, it is known that defective Merlin protein functionality leads to abnormal cell proliferation. Herein, we utilized a human induced pluripotent stem cell (hiPSC)-based Schwann cell (SC) model to investigate the role of merlin in human SCs. SCs were derived from hiPSCs carrying a NF2 mutation (c.191 T > C; p. L64P), its isogenic wild-type control cell line, and a NF2 patient-derived hiPSC line. NF2 mutant SCs showed abnormal cellular morphology and proliferation. Proteomic analyses identified novel interaction partners for Merlin - Arkadia and SKOR2. Our results established a new model in which merlin interacts with Arkadia and SKOR2 and this interaction is required for the proper activation of the SMAD-dependent pathway in TGF{beta} signaling.

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Tang, P.-C., Um, S., Mayfield, A. B., Bracho, O. R., Del Castillo, C., Dinh, C. T., Dykxhoorn, D. M., Liu, X. Z.. 2024-09-26. Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human.. https://doi.org/10.1101/2024.09.24.614711

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