Arp complex and CAPZA3 scaffold in sperm head found essential for fertilization in mice and humans
The authors report that knockout of Actrt2 or Actrt3 in mice disrupts perinuclear theca assembly and impairs sperm penetration of the zona pellucida in vitro.
A research group reported in the Proceedings of the National Academy of Sciences that the actin-related proteins (Arp) ACTRT2 and ACTRT3 are essential for fertilization in both humans and mice. doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗ The work examined how sperm structures form during spermatogenesis and why fertilization fails when they are disrupted.
Structural defects in sperm
Ultrastructural and immunofluorescence analyses showed that deficiency of ACTRT2 or ACTRT3 disrupts assembly of the subacrosomal layer of the perinuclear theca (SAL-PT). This leads to acrosome detachment and then to manchette abnormalities, which in turn impair formation of the postacrosomal sheath of the perinuclear theca. doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗
The structural defects were accompanied by reduced amounts of PAWP and PLCζ, candidate sperm-borne oocyte-activating factors. In in vitro fertilization, knockout of Actrt2 or Actrt3 severely impaired the ability of spermatozoa to penetrate the zona pellucida. doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗ According to the authors, ACTL10 is dispensable for fertility, while the human-specific ACTL8 may play a role in early spermatogenesis.
The Arp complex and CAPZA3 scaffold
ACTRT2, ACTRT3, ACTL7A, ACTL7B and ACTL9 form a testis-enriched Arp complex in the SAL-PT, and its members maintain one another's stability. doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗ The complex interacts with the perinuclear theca protein CAPZA3, which binds and stabilizes PLCζ.
doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗
The Arp complex also interacts with DPY19L2/FAM209-associated proteins, which mediate anchoring of the acrosome to the nuclear envelope. The authors describe a sequential scaffold of DPY19L2/FAM209-associated protein, Arp complex and CAPZA3 that extends from the nuclear envelope to the acrosome. doi.org
Proceedings of the National Academy of Sciencesdoi.orgOpen source ↗ They state that it is indispensable for fertilization and provides a basis for work on the diagnosis and treatment of fertilization failure.
