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Extraciliary OFD1 Is Involved in Melanocyte Survival through Cell Adhesion to ECM via Paxillin.
Kim, Nan-Hyung; Lee, Chang Hoon; Lee, Ai-Young.
Afiliação
  • Kim NH; Department of Dermatology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Ilsandong-gu, Goyang-si 10326, Republic of Korea.
  • Lee CH; College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea.
  • Lee AY; Department of Dermatology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Ilsandong-gu, Goyang-si 10326, Republic of Korea.
Int J Mol Sci ; 24(24)2023 Dec 15.
Article em En | MEDLINE | ID: mdl-38139355
ABSTRACT
Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral-facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. However, it remains unknown whether primary cilia are involved in the control of melanocyte apoptosis. While both intraflagellar transport 88 (IFT88) and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) are associated with ciliogenesis in melanocytes, only the knockdown of OFD1, but not IFT88 and RPGRIP1L, resulted in increased melanocyte apoptosis. OFD1 knockdown led to a decrease in the expression of proteins involved in cell-extracellular matrix (ECM) interactions, including paxillin. The OFD1 amino acid residues 601-1012 interacted with paxillin, while the amino acid residues 1-601 were associated with ciliogenesis, suggesting that the OFD1 domains responsible for paxillin binding are distinct from those involved in ciliogenesis. OFD1 knockdown, but not IFT88 knockdown, inhibited melanocyte adhesion to the ECM, a defect that was restored by paxillin overexpression. In summary, our findings indicate that the downregulation of OFD1 induces melanocyte apoptosis, independent of any impairment in ciliogenesis, by reducing melanocyte adhesion to the ECM via paxillin.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vitiligo / Adesão Celular / Paxilina / Melanócitos Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vitiligo / Adesão Celular / Paxilina / Melanócitos Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article