WDR64

WDR64 is a testis-specific WD40 repeat protein containing two β-propellers that dynamically localizes during spermiogenesis, associating with the manchette in elongating spermatids (steps 8–14) and subsequently relocating to the flagellum (steps 15–16) and the midpiece of mature spermatozoa (PMID:39386799). WDR64 forms a complex with the outer dense fiber protein ODF1, co-localizing at both the manchette during nuclear shaping and the midpiece of mature sperm, implicating it in manchette-mediated nuclear remodeling and flagellar assembly (PMID:39386799).

1. 2024 Medium

   The first characterization of WDR64 established it as a testis-specific WD40 protein with a dynamic localization pattern during spermiogenesis—moving from the manchette to the flagellum—and identified ODF1 as a physical binding partner, linking WDR64 to nuclear shaping and flagellar assembly.

   Evidence Immunofluorescence, RT-PCR, Western blot, and IP-MS in mouse testis and spermatozoa (single lab study)

   PMID:39386799

   Open questions at the time

   • No loss-of-function (knockout or knockdown) data demonstrating a requirement for WDR64 in spermiogenesis or fertility
   • WDR64–ODF1 interaction identified by IP-MS without reciprocal Co-IP or in vitro reconstitution
   • Structural basis for the two β-propeller domains and their individual contributions to localization or interaction is unknown

• Whether WDR64 is functionally required for sperm morphogenesis and male fertility remains untested, and the molecular mechanism by which the WDR64–ODF1 complex contributes to manchette-mediated nuclear shaping or flagellar midpiece assembly is unresolved.
• No genetic studies in animal models or human cohorts linking WDR64 mutations to infertility or spermiogenesis defects
• Downstream effectors or cargo transported by the WDR64–ODF1 complex are unidentified
• Regulatory mechanisms controlling WDR64 expression timing and dynamic relocalization are unknown