The Adhesion G-Protein-Coupled Receptor GPR115/<i>ADGRF4</i> Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1
Romy Winkler,
Marianne Quaas,
Stefan Glasmacher,
Uwe Wolfrum,
Torsten Thalheim,
Jörg Galle,
Knut Krohn,
Thomas M. Magin,
Gabriela Aust
Affiliations
Romy Winkler
Research Laboratories and Clinic of Orthopedic Surgery, Traumatology and Plastic Surgery, Leipzig University and University Hospital, 04103 Leipzig, Germany
Marianne Quaas
Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, Leipzig University and University Hospital, 04103 Leipzig, Germany
Stefan Glasmacher
Research Laboratories and Clinic of Orthopedic Surgery, Traumatology and Plastic Surgery, Leipzig University and University Hospital, 04103 Leipzig, Germany
Uwe Wolfrum
Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany
Torsten Thalheim
Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, 04107 Leipzig, Germany
Jörg Galle
Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, 04107 Leipzig, Germany
Knut Krohn
Core Unit DNA-Technologies, Leipzig University, 04103 Leipzig, Germany
Thomas M. Magin
Division of Cell and Developmental Biology, Institute of Biology, Leipzig University, 04103 Leipzig, Germany
Gabriela Aust
Research Laboratories and Clinic of Orthopedic Surgery, Traumatology and Plastic Surgery, Leipzig University and University Hospital, 04103 Leipzig, Germany
Among the 33 human adhesion G-protein-coupled receptors (aGPCRs), a unique subfamily of GPCRs, only ADGRF4, encoding GPR115, shows an obvious skin-dominated transcriptomic profile, but its expression and function in skin is largely unknown. Here, we report that GPR115 is present in a small subset of basal and in most suprabasal, noncornified keratinocytes of the stratified epidermis, supporting epidermal transcriptomic data. In psoriatic skin, characterized by hyperproliferation and delayed differentiation, the expression of GPR115 and KRT1/10, the fundamental suprabasal keratin dimer, is delayed. The deletion of ADGRF4 in HaCaT keratinocytes grown in an organotypic mode abrogates KRT1 and reduces keratinocyte stratification, indicating a role of GPR115 in epidermal differentiation. Unexpectedly, endogenous GPR115, which is not glycosylated and is likely not proteolytically processed, localizes intracellularly along KRT1/10-positive keratin filaments in a regular pattern. Our data demonstrate a hitherto unknown function of GPR115 in the regulation of epidermal differentiation and KRT1.
