Septins support sperm motility Free

The midpiece and the principal piece of the mammalian sperm tail are separated by the annulus – a fibrous structure composed of septin filaments. Here (p. 923), Pao-Lin Kuo and colleagues elucidate the structure of these filaments and their role in supporting sperm motility. They demonstrated that SEPT12 forms a complex with SEPT2, SEPT4, SEPT7 and SEPT6, and colocalised with these proteins at the annulus. The authors determined the exact order of these proteins within the filament, and found that SEPT2 and SEPT4, which belong to the same septin subgroup, are interchangeable. They then showed that SEPT12 molecules can interact through their N- and C-termini (potentially resulting in filament polymerisation), and that SEPT12 and the neighbouring SEPT7 subunit interacted through their GTP-binding domains (GBDs). Two mutations in the SEPT12 GBD that have been identified in infertile men (SEPT12-T89M and SEPT12-D197N) abrogated this interaction, and none of the five septins were localised at the annulus in sperm from an affected patient. Sperm from SEPT12-D197N homozygous mutant mice, like those of the human patient, showed morphological abnormalities and loss of septins from the annulus, coupled with reduced sperm motility. These results elucidate a potential aetiology of male infertility, the causes of which are often unclear.