# Arp complex and CAPZA3 scaffold in sperm head found essential for fertilization in mice and humans

- Published: 2026-11-05 22:04 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: fertilization failure, ACTRT2, ACTRT3, perinuclear theca, acrosome, zona pellucida, PLCζ, DPY19L2, actin-related proteins, knockout mice
- URL: https://realtech.media/news/rt-5c35b1cefecd7b541f3aef75_arp_complex_and/

**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.**

![Arp complex and CAPZA3 scaffold in sperm head found essential for fertilization in mice and humans](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/303d26100c4388c1.jpg)
*Theprevetvikng, Wikimedia Commons, CC BY 4.0*

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. [1] 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. [1]

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. [1] 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. [1] The complex interacts with the perinuclear theca protein CAPZA3, which binds and stabilizes PLCζ. [1]

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. [1] They state that it is indispensable for fertilization and provides a basis for work on the diagnosis and treatment of fertilization failure.

## Sources

1. [Proceedings of the National Academy of Sciences](https://doi.org/10.1073/pnas.2608548123)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-5c35b1cefecd7b541f3aef75_arp_complex_and/