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Author Notes:


Conceptualization: Yeon Ja Choi, Jiang Chen.

Data curation: Yeon Ja Choi, Ning Yang, Abraham Andreu-Cervera.

Formal analysis: Yeon Ja Choi, Jiang Chen.

Funding acquisition: Chuan Qin, Jiang Chen.

Investigation: Yeon Ja Choi, Abraham Andreu-Cervera, Jiang Chen.

Methodology: Yeon Ja Choi, Christine Laclef, Ning Yang, Abraham Andreu-Cervera, Joshua Lewis, Xuming Mao, Elizabeth R. Snedecor, Ken-Ichi Takemaru, Peter J. Koch, Aimee S. Payne, Andrew P. Kowalczyk.

Project administration: Chuan Qin.

Resources: Christine Laclef, Xuming Mao, Li Li, Ken-Ichi Takemaru, Chuan Qin, Sylvie Schneider-Maunoury, Yusuf A. Hannun, Peter J. Koch, Aimee S. Payne, Andrew P. Kowalczyk

Visualization: Abraham Andreu-Cervera, Jiang Chen.

Writing – original draft: Yeon Ja Choi.

Writing – review & editing: Christine Laclef, Sylvie Schneider-Maunoury, Kenneth R. Shroyer, Yusuf A. Hannun, Richard A. Clark, Aimee S. Payne, Andrew P. Kowalczyk, Jiang Chen.

We would like to thank Dr. Jiangli Chen for advice; Betty Wang, Chang-Kyung Kim, Xi (Cici) Chen, and Isabelle Anselme (SSM lab) for technical assistance.

We are grateful to Dr. Cungui Mao for cell lines, the animal and imaging facilities of the IBPS (Institut de Biologie Paris-Seine FR3631, Sorbonne Université, CNRS, Paris, France), and the Central Microscopy Imaging Center of Stony Brook University for support.


Research Funding:

This study was supported by start-up funds provided by the Department of Pathology and the Cancer Center of Stony Brook University, and research grants from NIH/NIAMS (AR061485 and AR071573 to JC, AR064220 to ASP, and AR048266 to APK) and National Natural Science Foundation of China (81773308 to JC and 81371731 to LL).

Work in the SSM lab was supported by funding from Sorbonne Université, Centre National pour la Recherche Scientifique, Institut National pour la Recherche Médicale, Agence Nationale pour la Recherche (ANR, project CILIAINTHEBRAIN to SSM) and Fondation ARC (PJA 20171206591 to SSM) and Fondation pour la Recherche Médicale (Equipe FRM DEQ20140329544 to SSM).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • HAIR
  • SKIN

RPGRIP1L is required for stabilizing epidermal keratinocyte adhesion through regulating desmoglein endocytosis

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Journal Title:

PLoS Genetics


Volume 15, Number 1


, Pages e1007914-e1007914

Type of Work:

Article | Final Publisher PDF


Cilia-related proteins are believed to be involved in a broad range of cellular processes. Retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) is a ciliary protein required for ciliogenesis in many cell types, including epidermal keratinocytes. Here we report that RPGRIP1L is also involved in the maintenance of desmosomal junctions between keratinocytes. Genetically disrupting the Rpgrip1l gene in mice caused intraepidermal blistering, primarily between basal and suprabasal keratinocytes. This blistering phenotype was associated with aberrant expression patterns of desmosomal proteins, impaired desmosome ultrastructure, and compromised cell-cell adhesion in vivo and in vitro. We found that disrupting the RPGRIP1L gene in HaCaT cells, which do not form primary cilia, resulted in mislocalization of desmosomal proteins to the cytoplasm, suggesting a cilia-independent function of RPGRIP1L. Mechanistically, we found that RPGRIP1L regulates the endocytosis of desmogleins such that RPGRIP1L-knockdown not only induced spontaneous desmoglein endocytosis, as determined by AK23 labeling and biotinylation assays, but also exacerbated EGTA- or pemphigus vulgaris IgG-induced desmoglein endocytosis. Accordingly, inhibiting endocytosis with dynasore or sucrose rescued these desmosomal phenotypes. Biotinylation assays on cell surface proteins not only reinforced the role of RPGRIP1L in desmoglein endocytosis, but also suggested that RPGRIP1L may be more broadly involved in endocytosis. Thus, data obtained from this study advanced our understanding of the biological functions of RPGRIP1L by identifying its role in the cellular endocytic pathway.

Copyright information:

© 2019 Choi et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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