G-Protein-gekoppelten-Rezeptoren (GPCRs) sind eine Gruppe von membranständigen Zellrezeptoren, welche extrazelluläre Signale mit Hilfe von Guanosintriphosphat (GTP)-bindenden Proteinen in intrazelluläre Signale umwandeln. Innerhalb der GPCR-Superfamilie bilden die Adhäsions-GPCR (aGPCR) mit 33 humanen Vertretern die zweitgrößte Familie [1]. Alle aGPCRs zeigen die gleiche Grundstruktur aus einer extrazellulären Domäne (ECD), die über sieben-Transmembrandomänen (7TM) mit der intrazellulären Domäne (ICD) verbunden ist. Eine Besonderheit stellt hierbei die außergewöhnliche Größe der ECD dar.

Skeletal muscle is a major organ comprising 30-40% of the human body mass. The coordination of processes resulting in mature muscle requires many genes, and their loss can result in debilitating muscle disorders. Of the strategies being developed to cure muscle diseases, enhancement of the natural process of muscle cell fusion in existing or introduced myogenic cells has great therapeutic potential. In this work, we determined whether a drug that stimulates proliferation and fusion of myoblasts could alleviate murine Duchenne muscular dystrophy. We also studied the necessity of a gene that is upregulated in early fusing human myoblast cultures and its role in muscle disease development.

Despite the immense functional relevance of GPR56 (gene ADGRG1) in highly diverse (patho)physiological processes such as tumorigenesis, immune regulation, and brain development, little is known about its exact tissue localization. Here, we validated antibodies for GPR56-specific binding using cells with tagged GPR56 or eliminated ADGRG1 in immunotechniques. Using the most suitable antibody, we then established the human GPR56 tissue expression profile. Overall, ADGRG1 RNA-sequencing data of human tissues and GPR56 protein expression correlate very well. In the adult brain especially, microglia are GPR56-positive. Outside the central nervous system, GPR56 is frequently expressed in cuboidal or highly prismatic secreting epithelia. High ADGRG1 mRNA, present in the thyroid, kidney, and placenta is related to elevated GPR56 in thyrocytes, kidney tubules, and the syncytiotrophoblast, respectively. GPR56 often appears in association with secreted proteins such as pepsinogen A in gastric chief cells and insulin in islet β-cells. In summary, GPR56 shows a broad, not cell-type restricted expression in humans.