Over the years, animal studies have identified astrotactins as important membrane proteins for glial-guided neuronal migration during central nervous system development and hair follicle polarity control during skin development. Biochemical studies have revealed intramembrane proteolysis as an important feature of astrotactins. The two fragments of astrotactins remain linked together by a disulfide bond after the proteolytic cleavage. In humans, mutations in astrotactin genes have also been linked to a wide range of diseases, including several developmental brain disorders, neurodegenerative diseases and cancer. In this review, I will summarize the current knowledge of the biological function of astrotactins in development, highlight the linkage between mutations in astrotactin genes and human disease and discuss several outstanding questions that remain unanswered. © 2017 IUBMB Life, 69(8):572-577, 2017.
Keywords: Astn1; Astn2; astrotactin; intramembrane proteolysis; neuronal migration; planar cell polarity.
© 2017 International Union of Biochemistry and Molecular Biology.