CATSPERG

CATSPERG is a single-pass transmembrane protein with a large extracellular domain that associates with the CATSPER ion channel complex in the principal piece of sperm flagella (PMID:19516020). Its stable expression depends on CATSPER1, as CATSPERG protein is lost in CATSPER1-knockout sperm, indicating that CATSPER1 is required for its trafficking and/or assembly into the complex (PMID:19516020). As a component of the CATSPER complex, CATSPERG contributes to the channel architecture essential for sperm hyperactivated motility and male fertility (PMID:19516020).

1. 2009 High

   Identification of CATSPERG as a novel transmembrane subunit of the CATSPER complex established that the channel includes auxiliary single-pass membrane proteins beyond the pore-forming CATSPER1-4 subunits, and revealed a hierarchical assembly mechanism in which CATSPER1 is required for CATSPERG stability.

   Evidence Co-immunoprecipitation from sperm lysates, immunofluorescence co-localization in wild-type vs. CATSPER1-knockout mouse sperm

   PMID:19516020

   Open questions at the time

   • Direct function of CATSPERG within the CATSPER complex (e.g., whether it modulates channel gating or ligand sensing) has not been determined
   • No CATSPERG-specific knockout model to assess its individual requirement for fertility
   • Structural basis of CATSPERG interaction with pore-forming CATSPER subunits is unknown

• The specific molecular role of CATSPERG — whether it functions as a ligand-binding accessory subunit, a structural scaffold, or a regulator of CATSPER channel activity — remains unknown.
• No CATSPERG-specific loss-of-function model exists
• No electrophysiological data on how CATSPERG affects CATSPER current properties
• No structural model of the CATSPERG extracellular domain or its binding interface with the complex