Discovery of a 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 are components of flagellar proteomes, how they translocate to flagella is unknown. Here we show that the expression pattern of the functionally nonannotated gene 4833427G06Rik (C11orf88), which is found only in vertebrates and is designated here as Hoatzin (Hoatz), suggests a functional association of its product with motile cilia and flagella. Hoatz knockout (KO) mice developed hydrocephalus and male infertility in an autosomal recessive manner, and the ependymal cilia frequently showed disorganized axonemes, reducing motility associated with collapsed spermatid flagella during cytodifferentiation. HOATZ was associated with certain proteins, including the flagellar glycolytic enzyme ENO4. In the testes of the Hoatz KO mice, the immature form of ENO4 accumulated in abnormal cytoplasmic puncta of developing spermatids. These data indicate that HOATZ is required for motile ciliogenesis and flagellar genesis in vertebrates by mediating the maturation of ENO4.