Affinage

MEIG1

Meiosis expressed gene 1 protein homolog · UniProt Q5JSS6

Length
88 aa
Mass
10.8 kDa
Annotated
2026-04-28
16 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MEIG1 is a small conserved protein essential for spermiogenesis, functioning as a scaffold within the manchette of elongating spermatids to coordinate cargo transport for sperm head shaping, flagellum assembly, and chromatin remodeling. PACRG recruits MEIG1 to the manchette via a hydrophobic interaction surface centered on residues W50, K57, F66, and Y68; MEIG1 reciprocally stabilizes PACRG against proteasomal degradation, and the MEIG1–PACRG complex directs downstream cargoes including SPAG16L and intraflagellar transport components IFT20 and IFT88 to the manchette (PMID:25715396, PMID:26726850, PMID:34673028, PMID:35257720). DNALI1 is additionally required for manchette localization of the MEIG1–PACRG complex, acting upstream to stabilize PACRG (PMID:37083624). Loss of MEIG1 in germ cells—but not in Sertoli cells or post-meiotic spermatids—disrupts manchette structure, abolishes sperm flagella formation, impairs histone-to-protamine chromatin remodeling, and causes complete male infertility (PMID:19805151, PMID:23258628, PMID:40035530).

Mechanistic history

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

    Before a physiological role was established, MEIG1 was found to exist as tyrosine-phosphorylated dimers that associate with meiotic chromosomes in primary spermatocytes, suggesting a nuclear role during meiotic prophase I.

    Evidence Subcellular fractionation and immunocytochemistry in developing mouse testis

    PMID:10642798

    Open questions at the time
    • Functional significance of chromosome association not determined
    • No evidence that phosphorylation regulates MEIG1 activity
    • Meiotic role not validated by loss-of-function
  2. 2009 High

    Knockout studies overturned the expected meiotic role, revealing that MEIG1 is dispensable for meiosis but essential for spermiogenesis—specifically for manchette integrity, spermatid elongation, and male fertility—and identifying PACRG as a binding partner whose stability depends on MEIG1.

    Evidence Germline Meig1 knockout mouse, TEM, co-immunoprecipitation

    PMID:19805151

    Open questions at the time
    • Mechanism by which MEIG1 maintains manchette structure unknown
    • Directionality of the MEIG1–PACRG interaction (who recruits whom) unresolved
  3. 2012 High

    Conditional knockouts established that MEIG1 functions cell-autonomously in germ cells (spermatocytes) rather than in Sertoli cells or post-meiotic spermatids, defining the critical cell type and developmental window.

    Evidence Cell-type-specific Cre-lox conditional knockouts (Hsp2a-Cre, Amh-Cre, Prm-Cre) with fertility and histology readouts

    PMID:23258628

    Open questions at the time
    • Molecular targets of MEIG1 in pre-meiotic spermatocytes not identified
    • Reason post-meiotic deletion has no effect (maternal protein perdurance?) not explored
  4. 2015 High

    Genetic epistasis across three knockout models resolved the recruitment hierarchy: PACRG recruits MEIG1 to the manchette (not vice versa), MEIG1 stabilizes PACRG, and SPAG16L is a downstream cargo whose manchette localization depends on both MEIG1 and PACRG.

    Evidence Reciprocal analysis in Meig1, Pacrg, and Spag16L knockout mice with immunofluorescence and yeast two-hybrid

    PMID:25715396

    Open questions at the time
    • How the MEIG1–PACRG complex physically transports SPAG16L cargo unknown
    • Other manchette cargoes not yet surveyed
  5. 2016 High

    Structural and mutagenesis studies mapped the MEIG1–PACRG binding interface to a contiguous hydrophobic patch (W50, K57, F66, Y68) on MEIG1, providing the first atomic-level understanding of how the complex assembles.

    Evidence Structure determination combined with systematic site-directed mutagenesis and bacterial co-expression stability assays

    PMID:26726850

    Open questions at the time
    • Full MEIG1–PACRG co-crystal structure not yet available at this point
    • Contribution of each residue to in vivo function not tested
  6. 2021 High

    Two advances solidified the structural and in vivo picture: the crystal structure of the PACRG–MEIG1 complex was solved showing PACRG's helical repeat fold engages MEIG1, and a CRISPR Y68 point-mutant mouse confirmed that this single residue is essential for manchette recruitment and fertility in vivo.

    Evidence X-ray crystallography of human PACRG–MEIG1 complex; CRISPR/Cas9 Y68 knock-in mice with immunofluorescence and fertility analysis

    PMID:33529594 PMID:34673028

    Open questions at the time
    • How PACRG simultaneously binds MEIG1 and microtubules in the manchette context not resolved
    • Why mutant MEIG1 Y68 accumulates at the acrosome is unexplained
  7. 2022 High

    The cargo repertoire was expanded to intraflagellar transport components: MEIG1 determines manchette localization of IFT20 and IFT88, linking the MEIG1–PACRG scaffold to flagellum biogenesis machinery.

    Evidence Co-immunoprecipitation from testis, reciprocal KO epistasis (Meig1 KO and conditional Ift20 KO), sucrose gradient fractionation

    PMID:35257720

    Open questions at the time
    • Whether MEIG1 binds IFT20/IFT88 directly or via PACRG is unclear
    • Full IFT cargo spectrum transported through the manchette not defined
  8. 2023 High

    DNALI1 was identified as an upstream factor required for manchette localization of the entire MEIG1–PACRG–SPAG16L module, acting by stabilizing PACRG, thus placing DNALI1 at the top of the recruitment hierarchy.

    Evidence Germ-cell-specific Dnali1 conditional KO mice, co-IP and pull-down with PACRG, immunofluorescence

    PMID:37083624

    Open questions at the time
    • Mechanism by which DNALI1 stabilizes PACRG is unknown
    • Whether DNALI1 is a structural manchette component or a transient stabilizer unclear
  9. 2025 Medium

    Beyond structural roles, MEIG1 was linked to sperm chromatin remodeling: ICSI with Meig1 KO sperm heads showed impaired fertilization and embryo development due to DNA damage from defective histone-to-protamine replacement.

    Evidence ICSI using Meig1 KO sperm heads, embryo development assay, sperm DNA damage assessment

    PMID:40035530

    Open questions at the time
    • Whether chromatin remodeling defect is a direct MEIG1 function or secondary to manchette disruption is unresolved
    • Molecular partners mediating chromatin remodeling role not identified
    • Single-lab finding not yet independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether MEIG1 has functions outside the male germline, how the MEIG1–PACRG scaffold physically translocates cargo along manchette microtubules, and whether human MEIG1 mutations cause male infertility.
  • No human genetic studies linking MEIG1 variants to infertility
  • Motor proteins mediating MEIG1-dependent manchette transport unidentified
  • Potential somatic functions entirely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005856 cytoskeleton 4 GO:0005694 chromosome 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474165 Reproduction 3
Partners
DNALI1IFT20IFT88PACRGSPAG16L
Complex memberships
MEIG1–PACRG complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 MEIG1 is essential for spermiogenesis (not meiosis): Meig1 knockout male mice are sterile due to impaired elongation and condensation of spermatids, with disruption of the manchette (a microtubular organelle required for sperm head and flagellar formation). MEIG1 also associates with PACRG protein, and testicular PACRG is reduced in MEIG1-deficient mice. Germline knockout mouse, transmission electron microscopy, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 19805151
1999 MEIG1 exists in multiple phosphorylated forms including tyrosine-phosphorylated dimers; the tyrosine-phosphorylated Mr 31,000 dimeric form localizes to the nuclear fraction coincident with meiotic prophase I and associates specifically with meiotic chromosomes in primary spermatocytes in vivo. Subcellular fractionation, immunocytochemistry, developmental time-course protein analysis Developmental biology Medium 10642798
2015 PACRG recruits MEIG1 to the manchette of elongating spermatids: MEIG1 no longer localizes to the manchette in Pacrg-deficient mice, while PACRG localization to the manchette is unchanged in Meig1-deficient mice. PACRG is unstable in mammalian cells but is stabilized by MEIG1 or proteasome inhibition. SPAG16L is a downstream cargo of the MEIG1/PACRG complex: SPAG16L fails to localize to the manchette in Meig1- or Pacrg-deficient mice, but MEIG1 and PACRG remain in the manchette of Spag16L-deficient mice. Genetic epistasis in knockout mice, immunofluorescence localization, yeast two-hybrid, proteasome inhibition assay Development (Cambridge, England) High 25715396
2021 Crystal structure of human PACRG in complex with MEIG1 was solved; PACRG adopts a helical repeat fold with a loop that interacts with MEIG1. Using the axonemal doublet microtubule structure and single-molecule fluorescence microscopy, PACRG was shown to bind microtubules while simultaneously recruiting free tubulin to catalyze inner junction formation. The homologous PACRG-like protein mediates dual tubulin interactions but does not bind MEIG1. X-ray crystallography, single-molecule fluorescence microscopy, structural modeling Structure (London, England : 1993) High 33529594
2016 MEIG1 adopts a unique fold providing a large surface for protein interactions; mutagenesis of 12 exposed conserved residues identified four (W50A, K57E, F66A, Y68A) that form a contiguous hydrophobic patch and dramatically reduce MEIG1 binding to PACRG. These four mutations also diminish MEIG1's ability to stabilize PACRG when co-expressed in bacteria. Site-directed mutagenesis, protein structure determination (NMR/crystallography implied), bacterial co-expression stability assay Scientific reports High 26726850
2012 MEIG1 regulates spermiogenesis through its action in germ cells (spermatocytes), not Sertoli cells or post-meiotic spermatids: germ-cell-specific (Hsp2a-Cre) Meig1 knockout recapitulates complete infertility, whereas Sertoli cell (Amh-Cre) or post-meiotic (Prm-Cre) Meig1 deletion has no significant effect on fertility or sperm parameters. Cell type-specific conditional knockout (Cre-lox), sperm count, motility, histology Andrology High 23258628
2021 Y68 of MEIG1 is required for PACRG to recruit MEIG1 to the manchette: CRISPR/Cas9 Y68 point mutant mice are completely infertile; mutant MEIG1 accumulates in the acrosome region of round spermatids and is absent from the manchette, as is the cargo SPAG16L, while PACRG localization in the manchette is unchanged. CRISPR/Cas9 knock-in point mutation in mice, immunofluorescence, sperm analysis, histology The Journal of biological chemistry High 34673028
2022 MEIG1 determines the manchette localization of IFT20 and IFT88 (intraflagellar transport components): in Meig1 knockout mice, IFT20 and IFT88 are absent from the manchette of elongating spermatids, shift to lighter sucrose gradient fractions, and their protein/mRNA levels are reduced; MEIG1 co-immunoprecipitates with IFT20 and IFT88 from testis extracts. Conversely, MEIG1 remains in the manchette in conditional Ift20 knockout mice. Co-immunoprecipitation from mouse testis, conditional knockout, immunofluorescence, sucrose gradient fractionation Developmental biology High 35257720
2023 DNALI1 recruits and stabilizes PACRG, and is required for formation of the MEIG1/PACRG complex within the manchette: in Dnali1 germ-cell-specific knockout mice, MEIG1, PACRG, and SPAG16L protein levels in testis are unchanged but their manchette localization is lost, leading to severe spermiogenic defects and male infertility. DNALI1 co-immunoprecipitates with and stabilizes PACRG. Co-immunoprecipitation, pull-down, conditional germ-cell-specific knockout mice, immunofluorescence, histology 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 showed significantly reduced fertilization and impaired embryo development to blastocyst, associated with severe sperm DNA damage, revealing a role for MEIG1 beyond spermiogenesis in sperm chromatin remodeling. ICSI with KO sperm heads, embryo development assay, 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 79 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