Intramembrane Proteolysis of Astrotactins

The study investigated the intramembrane proteolysis of astrotactins, specifically focusing on mouse astrotactin-2 (Astn2). Researchers found that Astn2 undergoes proteolytic cleavage in its second transmembrane domain (TM2), with a disulfide bond maintaining the connection between the resulting fragments. This proteolysis was shown to be insensitive to certain transmembrane domain replacements but was inhibited by others, such as the transmembrane domains of CD4 and the asialoglycoprotein receptor. The findings highlighted a unique transmembrane topology for astrotactins and identified specific substrate sequences necessary for the cleavage of type 2 transmembrane segments, contributing to the understanding of astrotactin maturation.