A DPY19L2/FAM209-associated protein-Arp complex-CAPZA3 scaffold is essential for perinuclear theca assembly and fertilization.

Loss of ACTRT2 or ACTRT3 disrupts SAL-PT assembly in human and mouse spermatogenesis, causing acrosome detachment, manchette defects, and impaired fertilization.

• Why it matters: Fertilization failure mechanisms are unclear, and the actin scaffolds that build the perinuclear theca and support sperm function are not well defined.
• What they did: Using ultrastructural and immunofluorescence analyses, the study tested ACTRT2/ACTRT3 deficiency in humans and mice and assessed sperm penetration in in vitro fertilization.
• The result: The defects reduce PAWP and PLCζ abundance and severely impair zona pellucida penetration, supporting a DPY19L2/FAM209-associated protein–Arp complex–CAPZA3 scaffold required for fertilization.

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