CBY3

CBY3 (Chibby3) is a regulator of sperm flagellum architecture that acts at the annulus to ensure correct positioning of the midpiece/principal piece junction (PMID:38197861). CBY3 forms a complex with the BAR-domain protein ciBAR1, and the two proteins colocalize to the sperm annulus near the curved membrane invagination at the flagellar pocket; this complex regulates local periannular membrane properties to halt annulus migration at the midpiece/principal piece boundary (PMID:38197861). Loss of CBY3 in mice causes the annulus to misposition into the principal piece and produces kinked flagella, linking CBY3 function to male fertility (PMID:38197861). Beyond this single coherent study, no further mechanistic detail for CBY3 has been characterized in the available corpus.

1. 2024 High

   Established that CBY3 partners with ciBAR1 at the sperm annulus to control where the annulus stops migrating, defining a membrane-shaping mechanism required for normal flagellar architecture.

   Evidence Mouse knockout of Cby3 or ciBAR1 with co-immunoprecipitation, colocalization imaging, and ultrastructural membrane analysis

   PMID:38197861

   Open questions at the time

   • The molecular basis by which the CBY3/ciBAR1 complex alters periannular membrane curvature or composition is not resolved
   • No structural model of the CBY3-ciBAR1 interface or of CBY3 domains is reported
   • Whether CBY3 has functions outside the sperm annulus is not addressed

• How the CBY3/ciBAR1 complex is recruited to the annulus and mechanistically halts annulus migration remains undefined.
• No upstream recruitment factor or post-translational regulation identified
• Direct biochemical activity of CBY3 on membranes not demonstrated