FUT8-mediated core fucosylation stabilizes TMEM67 to promote ciliogenesis.

Glycosylation of membrane proteins plays an essential role in diverse biological processes. However, it remains unknown whether this posttranslational modification occurs on ciliary membrane proteins. Herein, by mass spectrometry-based proteomic analysis, we demonstrate that multiple membrane proteins localized in the ciliary transition zone undergo core fucosylation, an N-linked glycosylation specifically catalyzed by fucosyltransferase 8 (FUT8). In-depth analysis reveals that FUT8 interacts with transmembrane protein 67 (TMEM67), a transition zone component closely linked to ciliopathies, and catalyzes its core fucosylation. Functional investigation shows that core fucosylation stabilizes TMEM67 by impeding its degradation via the autophagy pathway, thereby ensuring its proper localization to the transition zone to promote cilium formation. Fut8-deficient mice exhibit ciliary defects in multiple organs, such as the kidney, brain, and trachea. These findings uncover a critical role for TMEM67 core fucosylation in ciliogenesis and have important implications for the pathogenesis of ciliopathies.