Intramembrane Proteolysis of Astrotactins

The study investigated the intramembrane proteolysis of mouse Astrotactin-2 (Astn2), revealing that it undergoes cleavage in its second transmembrane domain, resulting in two fragments connected by a disulfide bond. This cleavage was specific to certain substrate sequences and was likely mediated by the SPP/SPPL family of proteases. The research highlighted the unique transmembrane topology of astrotactins and their role in neuron-glia interactions and hair follicle polarity, with Astn2 influencing hair follicle orientation in mice. The study also found that Astn2's proteolytic processing was a conserved event, with implications for neuronal development, and suggested that Astn1 might share similar structural features.