The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1

Abstract

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.

Enamel Phenotypes: Genetic and Environmental Determinants

“…Animal studies have added greatly to our knowledge of both normal and pathological enamel formation. The advent of transgenic animals has allowed for detailed studies of gene expression, protein function, pathogenic mechanisms, and detailed phenotyping that would not be possible in humans [ 30 , 31 , 32 ]. For example, many studies assessed tooth enamel genes (e.g., AmelX , Enam , Mmp20 ) and different mutations, the resulting proteins, and how and why these changes were associated with different enamel phenotypes [ 33 , 34 , 35 ].…”

Correction: Winkler et al. The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1. Cells 2022, 11, 3151

“…In the original publication [1], the figures were not sharp enough. The enhanced Figures 1-6 appear below.…”

“…In the original publication [ 1 ], the figures were not sharp enough. The enhanced Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6 appear below.…”