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

Autor:	Tang PC; Equal contribution: Pei-Ciao Tang and Seyoung Um.; Lead contact: Pei-Ciao Tang.; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States., Um S; Equal contribution: Pei-Ciao Tang and Seyoung Um.; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States., Mayfield AB; Coral Reef Diagnostics., Bracho OR; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States., Castillo CD; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States., Dinh CT; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.; Sylvester Comprehensive Cancer Center, Miami, FL, 33136, United States., Dykxhoorn DM; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, United States., Liu XZ; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.; Dr. John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 26. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1101/2024.09.24.614711
Abstrakt:	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 TGFβ signaling. Competing Interests: Declaration of interests The authors declare no competing interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu