FUT8 Regulates Cerebellar Neurogenesis and Development Through Maintaining the Level of Neural Cell Adhesion Molecule...

Core fucosylation at N-glycans, which is uniquely catalyzed by fucosyltransferase FUT8, plays essential roles in post-translational regulation of protein function. Aberrant core fucosylation leads to neurological disorders in individuals with congenital glycosylation disorders (CDG). However, the underlying mechanisms for these neurological defects remain largely unknown. In this study, we have showed that FUT8 and fucosylation are abundant in cerebellum. Specific deletion of Fut8 in cerebellar granule neuron progenitors (GNPs) results in the impaired proliferation and differentiation of GNPs, as well as the compromised neuronal development, synaptic physiology and motor coordination. Mechanistically, we have showed that Fut8 deficiency reduced Contactin 2 (Cntn2) expression, a member of neural cell adhesion molecules (NCAMs). Furthermore, ectopic Cntn2 can rescue the neuronal defects induced by Fut8 deficiency. Collectively, our study has revealed the important roles of FUT8 and core fucosylation in regulating cerebellar development and function through modulating Cntn2 expression.