Affinage

ACTRT3

Actin-related protein T3 · UniProt Q9BYD9

Length
372 aa
Mass
41.0 kDa
Annotated
2026-06-09
6 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACTRT3 (ARPM1) is a testis-enriched actin-related protein that functions as a structural component of the spermatid perinuclear theca (PT) required for acrosome biogenesis and male fertility (PMID:41668650). It forms a testis-specific complex with profilin III (PFN3), a partnership that is mutually stabilizing: PFN3 is required to maintain ARPM1 in the nuclear fraction, and loss of either partner reduces the level of the other (PMID:18692047, PMID:34869336, PMID:41668650). Within the PT, ACTRT3 associates with the scaffold proteins ACTRT1, ACTRT2, ACTL7A and SPEM2 and with the sperm-surface protein ZPBP, positioning it as a PT scaffold component that mediates ZPBP localization [PMID:41668650, PMID:bio_10.1101_2025.03.27.645694]. ACTRT3 supports acrosome development by sustaining Golgi trafficking—its loss reduces TGN46 and GOPC, mislocalizes GM130, and impairs autophagic flux (LC3B, CTSB, mTOR)—and it remodels the actin cytoskeleton, interacting with the regulators CFL1 and CNN1 and altering F-actin distribution and cell shape when overexpressed (PMID:41668650). Loss of ACTRT3 in mice causes subfertility with acrosomal defects beginning at the cap phase [PMID:41668650, PMID:bio_10.1101_2025.03.27.645694].

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2008 Medium

    Established ACTRT3 as a haploid germ-cell-specific actin-related protein with a dynamic nuclear localization and identified its first binding partner, addressing what protein context it operates in.

    Evidence Co-immunoprecipitation and immunolocalization across spermiogenesis in mouse testis

    PMID:18692047

    Open questions at the time
    • Functional consequence of the PFN3 interaction not tested
    • No loss-of-function phenotype established
    • Single lab, reciprocal validation limited
  2. 2021 Medium

    Defined the directionality of the PFN3-ARPM1 relationship, showing PFN3 stabilizes ARPM1 and is required for its nuclear localization, resolving how the complex is maintained.

    Evidence Pfn3 CRISPR/Cas9 knockout mice with subcellular fractionation and western blot

    PMID:34869336

    Open questions at the time
    • Mechanism of ARPM1 degradation upon PFN3 loss unknown
    • Direct downstream function of the complex not addressed
  3. 2025 Medium

    Placed ARPM1 in the perinuclear theca as a scaffold tethering PFN3 and linked its loss to acrosomal defects and disrupted Golgi trafficking, addressing the cellular pathway it serves.

    Evidence Arpm1 knockout mouse, co-IP, immunofluorescence and western blot (preprint)

    PMID:bio_10.1101_2025.03.27.645694

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Direct vs. indirect effect on Golgi markers not dissected
    • Mechanism of ZPBP localization not resolved
  4. 2026 High

    Consolidated ACTRT3 as a PT scaffold coordinating Golgi trafficking, autophagic flux, and actin remodeling for acrosome biogenesis, integrating its protein interactions with a defined fertility phenotype.

    Evidence Actrt3 knockout mouse phenotyping, co-IP, mass spectrometry, HEK293T overexpression, immunofluorescence, western blot

    PMID:41668650

    Open questions at the time
    • Whether ACTRT3 directly regulates autophagy or acts indirectly is unresolved
    • Catalytic/structural role of the actin-related fold not defined
    • CFL1/CNN1 interactions are MS-enriched and not functionally validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ACTRT3 mechanistically couples PT architecture to Golgi-derived acrosome assembly and F-actin dynamics remains unresolved.
  • No structural model of ACTRT3 within the PT scaffold
  • Direct molecular link between ACTRT3 and Golgi trafficking machinery unknown
  • Whether cytoskeletal remodeling is upstream or downstream of acrosome defects untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005634 nucleus 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-9612973 Autophagy 1
Partners
ACTL7AACTRT1ACTRT2CFL1CNN1PFN3SPEM2ZPBP
Complex memberships
perinuclear theca

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Mouse ArpM1 (ACTRT3) is expressed exclusively in the testis in haploid germ cells; it localizes to the nucleus during spermiogenesis and dynamically changes its nuclear localization. Co-immunoprecipitation identified profilin III (PFN3) as an ArpM1-interacting protein, forming a testis-specific complex implicated in sperm nucleus organization. Co-immunoprecipitation, immunolocalization during spermiogenesis FEBS letters Medium 18692047
2021 In Pfn3-knockout mice, ARPM1 (ACTRT3) is absent from the nuclear fraction of testes and sperm, indicating that PFN3 stabilizes ARPM1 and that the PFN3-ARPM1 complex is required for ARPM1 nuclear localization. Loss of PFN3 leads to degradation of ARPM1. CRISPR/Cas9 knockout, subcellular fractionation, western blot Frontiers in cell and developmental biology Medium 34869336
2026 ACTRT3 localizes to the perinuclear theca (PT) of murine spermatids. Actrt3-/- male mice are subfertile with acrosome biogenesis defects beginning at cap phase. Loss of ACTRT3 reduces TGN46 and GOPC protein levels, mislocalizes GM130, and impairs autophagy markers (LC3B, CTSB, mTOR), indicating disrupted Golgi trafficking and autophagic flux required for acrosome development. Co-IP revealed interaction with PT proteins ACTRT1, ACTRT2, ACTL7A, SPEM2, and sperm surface protein ZPBP. Mass spectrometry identified cytoskeletal regulators CFL1 and CNN1 as enriched interactors. Overexpression of Actrt3 in HEK293T cells altered cell shape and F-actin filament distribution, demonstrating a role in cytoskeletal remodeling. PFN3 protein levels were significantly reduced in Actrt3-/- mice. Knockout mouse model, co-immunoprecipitation, mass spectrometry, immunofluorescence localization, overexpression in HEK293T cells, western blot Development (Cambridge, England) High 41668650
2025 ARPM1/ACTRT3 localizes to the perinuclear theca of round and elongating spermatids. Arpm1-/- male mice are subfertile with acrosomal morphological aberrations from cap phase. Loss of ARPM1 deregulates GM130 and TGN46, indicating defects in cis- and trans-Golgi trafficking. Co-IP confirmed interactions with PT proteins ACTRT1, ACTRT2, ACTL7A, and sperm surface protein ZPBP (in addition to the previously shown PFN3 interaction). ARPM1 is proposed to act as a structural PT scaffold component tethering PFN3 to regulate Golgi-related acrosome development and mediating ZPBP localization for fertilization. Knockout mouse model, co-immunoprecipitation, immunofluorescence, western blot bioRxivpreprint Medium bio_10.1101_2025.03.27.645694

Source papers

Stage 0 corpus · 6 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Nuclear localization of profilin III-ArpM1 complex in mouse spermiogenesis. FEBS letters 26 18692047
2021 Loss of Profilin3 Impairs Spermiogenesis by Affecting Acrosome Biogenesis, Autophagy, Manchette Development and Mitochondrial Organization. Frontiers in cell and developmental biology 21 34869336
2024 Plasma genome-wide mendelian randomization identifies potentially causal genes in idiopathic pulmonary fibrosis. Respiratory research 6 39425105
2026 Actin-related protein T3 is required for acrosome biogenesis and sperm function in mice. Development (Cambridge, England) 0 41668650
2026 Regulatory Variation at TERT and TERC Shows Limited Association with Early-Onset Alzheimer's Disease in Carriers of the Mexican Founder Mutation PSEN1 A431E. Medical sciences (Basel, Switzerland) 0 42201020
2020 Assessment of the genes and molecular mechanisms of B cells activation through systems biology approaches. Human antibodies 0 31524152

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