Affinage

MEIG1

Meiosis expressed gene 1 protein homolog · UniProt Q5JSS6

Length
88 aa
Mass
10.8 kDa
Annotated
2026-06-10
16 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MEIG1 is a small conserved protein essential for spermiogenesis that functions as an intramanchette transport hub coordinating sperm flagellum assembly and sperm chromatin remodeling (PMID:20004656, PMID:25715396). Genetic ablation in mice causes complete male infertility with disrupted manchette structure, loss of elongated spermatids, and immotile sperm, and conditional knockouts establish that this requirement is intrinsic to germ cells (spermatocytes) rather than Sertoli cells or post-meiotic spermatids (PMID:19805151, PMID:23258628). Within the manchette of elongating spermatids, MEIG1 forms a complex with PACRG, which recruits MEIG1 to the manchette and is in turn stabilized by MEIG1 against proteasomal degradation (PMID:25715396); structural and mutagenesis work shows MEIG1 adopts a fold presenting a contiguous hydrophobic patch (W50, K57, F66, Y68) that mediates PACRG binding, with the Y68 residue required in vivo for manchette recruitment (PMID:26726850, PMID:33529594, PMID:34673028). The MEIG1/PACRG complex acts upstream to determine the manchette localization of downstream cargos—SPAG16L and the intraflagellar transport components IFT20 and IFT88—needed to build the sperm flagellum, while DNALI1 functions upstream to localize the MEIG1/PACRG complex itself to the manchette (PMID:25715396, PMID:35257720, PMID:37083624). MEIG1-dependent manchette function is additionally required for proper sperm chromatin packaging, as knockout sperm exhibit severe DNA damage and yield poor embryo development after ICSI (PMID:40035530). In meiotic spermatocytes, a tyrosine-phosphorylated dimeric form of MEIG1 enters the nucleus and associates with meiotic chromosomes (PMID:10642798).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 Medium

    Established that MEIG1 exists in distinct phosphorylated and dimeric forms with form-specific subcellular targeting, raising the question of how a single small protein partitions between nucleus and cytoplasm during meiosis.

    Evidence Subcellular fractionation and in vivo immunocytochemistry across testicular developmental stages

    PMID:10642798

    Open questions at the time
    • Function of the chromosome-associated nuclear form during meiosis not defined
    • Kinase responsible for tyrosine phosphorylation unidentified
    • No molecular partners established at this stage
  2. 2009 High

    Defined MEIG1 as essential for spermiogenesis rather than meiosis and identified PACRG as a physical partner whose protein levels depend on MEIG1, linking MEIG1 loss to manchette disruption and male sterility.

    Evidence Meig1 knockout mice with TEM of the manchette, co-immunoprecipitation, and Western blot of PACRG in KO testes

    PMID:19805151 PMID:20004656

    Open questions at the time
    • Direct vs indirect basis of PACRG reduction not yet resolved
    • Manchette cargos not identified
    • Whether MEIG1 acts in germ cells or somatic support cells unresolved
  3. 2012 High

    Localized the cell-autonomous requirement for MEIG1 to spermatocytes, ruling out Sertoli cell and post-meiotic spermatid functions and establishing where in the lineage MEIG1 acts.

    Evidence Cell-type-specific conditional knockouts with Hsp2a-Cre, Prm-Cre, and Amh-Cre drivers and fertility/sperm readouts

    PMID:23258628

    Open questions at the time
    • Molecular mechanism downstream of germ-cell MEIG1 not addressed
    • Timing of MEIG1 action relative to manchette assembly unclear
  4. 2015 High

    Resolved the directionality of the MEIG1–PACRG relationship, showing PACRG recruits MEIG1 to the manchette while MEIG1 stabilizes PACRG, and identified SPAG16L as the first downstream transport cargo of the complex.

    Evidence Yeast two-hybrid, immunofluorescence colocalization, genetic epistasis across Meig1-/-, Pacrg-/-, and Spag16L-/- mice, and proteasome inhibitor stability assays

    PMID:25715396

    Open questions at the time
    • Full cargo repertoire of the complex not defined
    • Structural basis of MEIG1–PACRG binding not yet known
  5. 2016 High

    Provided the structural basis of MEIG1 function, defining a unique fold and a contiguous hydrophobic patch (W50, K57, F66, Y68) required for PACRG binding and PACRG stabilization.

    Evidence Structural determination of the MEIG1 fold with systematic site-directed mutagenesis and bacterial co-expression stability assays

    PMID:26726850

    Open questions at the time
    • Interface validated in bacteria but not in vivo at this stage
    • Structure of the bound PACRG complex not yet solved
  6. 2021 High

    Defined the PACRG–MEIG1 complex architecture at atomic resolution and tested individual interface residues in vivo, showing PACRG's helical repeat fold engages MEIG1 and that Y68 of MEIG1 is required for manchette recruitment and fertility.

    Evidence X-ray crystallography of the PACRG–MEIG1 complex with single-molecule fluorescence microscopy, plus CRISPR/Cas9 Y68A knock-in mice with localization and fertility phenotyping

    PMID:33529594 PMID:34673028

    Open questions at the time
    • Mechanistic link between PACRG tubulin/axoneme interactions and the spermatid manchette role not fully reconciled
    • Cause of aberrant MEIG1 acrosomal accumulation in Y68 mutants unexplained
  7. 2022 High

    Expanded the cargo set of the MEIG1/PACRG transport hub to include IFT20 and IFT88, placing MEIG1 upstream of IFT machinery delivery to the manchette.

    Evidence Co-immunoprecipitation from testis, immunofluorescence in Meig1 KO and conditional Ift20 KO mice, and sucrose gradient fractionation

    PMID:35257720

    Open questions at the time
    • Direct vs indirect MEIG1–IFT interactions not distinguished
    • How cargo selection is achieved mechanistically unknown
  8. 2023 High

    Identified DNALI1 as an upstream factor required to localize the MEIG1/PACRG complex to the manchette, extending the regulatory hierarchy beyond the MEIG1–PACRG dyad.

    Evidence Reciprocal co-immunoprecipitation/pull-down and immunofluorescence in Dnali1 conditional KO mice with Western blot

    PMID:37083624

    Open questions at the time
    • Whether DNALI1 acts on PACRG or MEIG1 directly not fully resolved
    • Mechanism of complex tethering to the manchette unknown
  9. 2025 Medium

    Connected MEIG1 manchette function to sperm chromatin remodeling and embryonic competence, showing that MEIG1 loss causes sperm DNA damage and poor embryo development.

    Evidence ICSI with Meig1 KO sperm heads, blastocyst development assay, and sperm DNA damage assessment

    PMID:40035530

    Open questions at the time
    • Direct molecular step of histone-to-protamine exchange not dissected
    • Single study without independent replication
    • Mechanistic link between manchette transport and chromatin packaging not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the meiotic nuclear/chromosome-associated form of MEIG1 mechanistically relates to its later manchette transport function remains unresolved.
  • No molecular partners identified for the chromosome-associated nuclear form
  • Functional consequence of meiotic chromosome association undefined
  • Regulation switching MEIG1 between meiotic and spermiogenic roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005694 chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1474165 Reproduction 2
Partners
DNALI1IFT20IFT88PACRGSPAG16L
Complex memberships
MEIG1/PACRG complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MEIG1 exists in multiple phosphorylated forms including two dimeric forms (Mr 31,000 and 32,000); the tyrosine-phosphorylated Mr 31,000 dimeric form localizes to the nuclear fraction of testicular protein extract and associates specifically with meiotic chromosomes in primary spermatocytes in vivo, whereas the Mr 32,000 dimeric form and monomeric forms remain cytoplasmic. Subcellular fractionation, immunocytochemistry, developmental staging of nuclear appearance Developmental biology Medium 10642798
2009 MEIG1 is essential for spermiogenesis (elongation and condensation stage) but not for meiosis; MEIG1-deficient mice are male-sterile with a disrupted manchette (microtubular organelle for sperm head/flagellar formation). MEIG1 associates with PACRG protein, and testicular PACRG protein is reduced in MEIG1-deficient mice. Meig1 gene knockout, transmission electron microscopy, co-immunoprecipitation/protein association assay, Western blot of PACRG in KO testes Proceedings of the National Academy of Sciences of the United States of America High 19805151
2009 Meig1 knockout mice show complete male infertility with absence of mature elongated spermatids and severely abnormal immotile sperm; additionally, delayed kinetics of meiotic stages and increased apoptosis of meiotic spermatocytes and round spermatids were observed, suggesting a secondary involvement in meiosis. Meig1 knockout mouse (elimination of common coding region), histology, sperm analysis, TUNEL/apoptosis assays Developmental biology High 20004656
2012 MEIG1 regulates spermiogenesis specifically through its function in germ cells (spermatocytes), not in Sertoli cells or post-meiotic spermatids; disruption of Meig1 in spermatocytes (Hsp2a-Cre) causes sterility mirroring global KO, whereas disruption in post-meiotic spermatids (Prm-Cre) or Sertoli cells (Amh-Cre) does not impair fertility or sperm production. Cell-type-specific conditional knockout using Cre/lox with Hsp2a-Cre, Prm-Cre, and Amh-Cre drivers; sperm count, motility, histology Andrology High 23258628
2015 MEIG1 and PACRG form a complex in the manchette of elongating spermatids; PACRG recruits MEIG1 to the manchette (MEIG1 fails to localize to manchette in Pacrg-deficient mice); MEIG1 (or proteasome inhibition) stabilizes PACRG against proteasomal degradation; SPAG16L is a downstream cargo of the MEIG1/PACRG complex (SPAG16L fails to localize to manchette in Meig1- or Pacrg-deficient mice, but MEIG1 and PACRG are still present in Spag16L-deficient manchette). Yeast two-hybrid, immunofluorescence colocalization in WT and KO mice, genetic epistasis using Meig1-/-, Pacrg-/-, and Spag16L-/- mice, proteasome inhibitor treatment, protein stability assays Development (Cambridge, England) High 25715396
2016 MEIG1 adopts a unique fold providing a large protein-protein interaction surface; four conserved residues (W50, K57, F66, Y68) form a contiguous hydrophobic patch critical for PACRG binding — alanine/glutamate substitutions at these positions dramatically reduce PACRG binding and abolish MEIG1's ability to stabilize PACRG in bacteria. NMR/structural determination of MEIG1 fold, site-directed mutagenesis of 12 conserved surface residues, binding assays, bacterial co-expression stability assay Scientific reports High 26726850
2021 Crystal structure of human PACRG in complex with MEIG1 revealed that PACRG adopts a helical repeat fold with a loop that interacts with MEIG1; structural modeling and single-molecule fluorescence microscopy suggest PACRG binds doublet microtubules while simultaneously recruiting free tubulin to catalyze inner junction formation in the axoneme; the homologous PACRG-like protein mediates dual tubulin interactions but does not bind MEIG1. X-ray crystallography (crystal structure of PACRG–MEIG1 complex), single-molecule fluorescence microscopy, structural comparison with Chlamydomonas axonemal doublet cryo-EM map Structure (London, England : 1993) High 33529594
2021 Y68 of MEIG1 is required for PACRG to recruit MEIG1 to the manchette; CRISPR/Cas9-generated Y68 point mutant mice are completely infertile with severely reduced sperm count; mutant MEIG1 accumulates aberrantly in the acrosome region of round spermatids and fails to localize to the manchette; the cargo SPAG16L also fails to reach the manchette, but PACRG localization is unaffected in these mutants. CRISPR/Cas9 knock-in point mutation (Y68A), male fertility assay, sperm count/morphology, immunofluorescence staining for manchette localization of MEIG1, PACRG, SPAG16L The Journal of biological chemistry High 34673028
2022 MEIG1 determines the manchette localization of intraflagellar transport (IFT) components IFT20 and IFT88; in Meig1 knockout mice, IFT20 and IFT88 are absent from the manchette of elongating spermatids and drift to lighter sucrose gradient fractions, indicating loss of complex association; MEIG1 co-immunoprecipitates with IFT20 and IFT88 from mouse testis extracts; conversely, MEIG1 manchette localization is unaffected in conditional Ift20 KO mice, placing MEIG1 upstream of IFT20/88. Co-immunoprecipitation from mouse testis, immunofluorescence in WT and Meig1 KO and conditional Ift20 KO mice, sucrose gradient fractionation Developmental biology High 35257720
2023 DNALI1 interacts with PACRG (recruits and stabilizes PACRG) within the manchette, and is required for the localization of the MEIG1/PACRG complex to the manchette; in Dnali1 conditional KO mice, testicular levels of MEIG1, PACRG, and SPAG16L are unchanged but their manchette localization is greatly disrupted, placing DNALI1 as an upstream regulator of MEIG1/PACRG complex formation at the manchette. Co-immunoprecipitation, pull-down assays, immunofluorescence in WT and Dnali1 conditional KO mice, Western blot eLife High 37083624
2025 MEIG1 plays a role in sperm chromatin remodeling (histone-to-protamine replacement) via the manchette; ICSI using sperm heads from Meig1 KO mice shows significantly reduced fertilization, poor blastocyst development, and severe sperm DNA damage, indicating MEIG1-mediated manchette function is required for proper sperm chromatin packaging necessary for normal embryogenesis. ICSI with Meig1 KO sperm heads, embryo development assay to blastocyst stage, sperm DNA damage assessment FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 40035530

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 MEIG1 is essential for spermiogenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 80 19805151
2015 A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella. Development (Cambridge, England) 50 25715396
2009 Meig1 deficiency causes a severe defect in mouse spermatogenesis. Developmental biology 21 20004656
2021 Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding. Structure (London, England : 1993) 20 33529594
1999 MEIG1 localizes to the nucleus and binds to meiotic chromosomes of spermatocytes as they initiate meiosis. Developmental biology 20 10642798
2016 Dissecting the structural basis of MEIG1 interaction with PACRG. Scientific reports 14 26726850
2023 DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice. eLife 13 37083624
1999 Two alternatively spliced Meig1 messenger RNA species are differentially expressed in the somatic and in the germ-cell compartments of the testis. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 12 9950214
2022 MEIG1 determines the manchette localization of IFT20 and IFT88, two intraflagellar transport components in male germ cells. Developmental biology 11 35257720
2012 Germ cell-specific disruption of the Meig1 gene causes impaired spermiogenesis in mice. Andrology 11 23258628
2021 A single amino acid mutation in the mouse MEIG1 protein disrupts a cargo transport system necessary for sperm formation. The Journal of biological chemistry 8 34673028
2022 Molecular dynamics study reveals key disruptors of MEIG1-PACRG interaction. Proteins 3 36444670
2022 Identification and functional analysis of Tex11 and Meig1 in spermatogenesis of Hyriopsis cumingii. Frontiers in physiology 2 36091389
2025 Normal embryo development needs MEIG1-mediated sperm formation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40035530
2025 In Silico Discovery of Potential Inhibitors Targeting the MEIG1-PACRG Complex for Male Contraceptive Development. Proteins 0 40265567
2024 In silico discovery of potential inhibitors targeting the MEIG1-PACRG complex for male contraceptive development. bioRxiv : the preprint server for biology 0 39763986

Missed literature

Know a paper Affinage missed for MEIG1? Flag it for the maintainers and the community.

No submissions yet.