Discovery of Vertebrate-Specific Factor that Processes Flagellar Glycolytic Enolase During Motile Ciliogenesis

Motile cilia and flagella require ATP for their formation and function. Although glycolytic enzymes have been found in flagellar proteomes, it remains unknown how they translocate into these motile organelles. Here, we characterized Hoatzin, a functionally non-annotated gene found only in vertebrates. Their expression pattern suggested a functional association with motile cilia and flagella. The knockout mouse developed hydrocephalus and male infertility in an autosomal recessive manner. In the null mutant, the ependymal cilia frequently showed disorganized axoneme, causing reduced motility, and the spermatid flagella collapsed during cytodifferentiation. Interestingly, HOATZ was found to be associated with various proteins, including a flagellar glycolytic enzyme, ENO4. In the null mutant testis, the immature form of ENO4 accumulated in abnormal cytoplasmic puncta of developing spermatids. Overall, these data indicate that HOATZ is a cytoplasmic factor that plays a critical role in motile ciliogenesis and flagellogenesis in vertebrates by mediating the maturation of ENO4.