| 2010 |
SPAG4L (SUN5) and SPAG4L-2 are transmembrane proteins that localize to the inner nuclear membrane, specifically restricted to the apical nuclear region of round spermatids facing the acrosomic vesicle, suggesting involvement in linkage of the acrosomic vesicle to the spermatid nucleus and acrosome biogenesis. |
Molecular dissection, cytological and biochemical investigations, immunofluorescence localization |
Molecular human reproduction |
Medium |
21159740
|
| 2011 |
SPAG4L (SUN5) localizes to the nuclear envelope and endoplasmic reticulum; the transmembrane region and coiled-coil domain (but not the SUN domain) are required for NE/ER localization. It is expressed during meiosis I and II, suggesting a role in NE reconstitution and nuclear migration during spermatocyte division. |
GFP-fusion subcellular localization, deletion analysis, Western blot, immunofluorescence with organelle markers |
DNA and cell biology |
Medium |
21711156
|
| 2015 |
Sun5 (Spag4l) transits through different cellular compartments during spermatogenesis: in pachytene spermatocytes it is in a membranous compartment distinct from the ER; in round spermatids it progresses to the Golgi and NE; in epididymal sperm it localizes to the tail/head junction. Sun5 is excluded from the NE facing the acrosome (negative result: Sun5 is NOT involved in acrosome attachment to the NE). In Dpy19l2 KO spermatids, upon acrosome detachment, Sun5 relocalizes to the entire NE. Sun5 is glycosylated. |
Immunohistochemistry, Western blot, Dpy19l2 knockout mouse model |
PloS one |
Medium |
25775128
|
| 2017 |
Homozygous loss-of-function deletion of SUN5 (frameshift p.Leu143Serfs*30) causes acephalic spermatozoa syndrome; the p.Gly114Arg variant has a strong inhibitory effect on SUN5 mRNA splicing in HeLa cells, establishing that loss of SUN5 function causes the acephalic spermatozoa/head-tail junction defect. |
Genomic sequencing, splicing assay in HeLa cells (minigene/splicing reporter) |
Human molecular genetics |
High |
28541472
|
| 2018 |
SUN5 interacts with the coupling apparatus protein DNAJB13 during spermatogenesis; SUN domain missense substitutions associated with acephalic spermatozoa syndrome impair this interaction. Mutations also affect secondary structure, protein folding, and cellular localization of SUN5. An intronic mutation causes aberrant splicing yielding a premature stop codon and truncated SUN5. |
Co-immunoprecipitation, artificial splicing system, mutagenesis, cellular localization assays |
The Journal of biological chemistry |
High |
29298896
|
| 2018 |
SUN5 truncation mutation (c.381delA; p.V128Sfs*7) decreases SUN5 protein expression and alters the distribution of ODF1 (outer dense fiber 1 protein) in sperm, linking SUN5 to organization of sperm neck structural components. |
Western blot, immunofluorescence of ODF1 in patient sperm |
Gene |
Low |
29331481
|
| 2019 |
SPAG4L (SUN5) and its shorter transcript variant SPAG4Lβ interact with Nesprin2 (a KASH domain protein) to form LINC complexes; these LINC complexes are involved in spermatocyte division during meiosis. |
Co-immunoprecipitation, immunofluorescence, northern blot, RT-PCR, in situ hybridization |
Acta biochimica et biophysica Sinica |
Medium |
31144711
|
| 2021 |
Sun5 knockout mice exhibit acephalic spermatozoa syndrome; the head-tail coupling apparatus (HTCA) and centrosome become distant from the nucleus at steps 9–10 of spermatid elongation, and head-tail separation occurs at steps 13–14. SUN5 interacts with Nesprin3 (confirmed by Co-IP) to form a LINC complex required for sperm head-tail connection; loss of Sun5 causes Nesprin3 to lose its localization at the posterior implantation fossa of the nucleus, leading to centrosome detachment. Downregulation of ODF1 and ODF2 also contributes to head-tail linkage damage. |
Sun5 knockout mouse generation, Co-immunoprecipitation, immunofluorescence, ultrastructural imaging, isobaric tag quantitative proteomics |
Frontiers in cell and developmental biology |
High |
34268309
|
| 2021 |
SUN5, Nesprin3, and ODF1 interact with each other (each pairwise combination confirmed by Co-IP in transfected HEK293T cells), forming a 'triplet' structural complex at the sperm neck; loss of SUN5 disrupts localization of both ODF1 and Nesprin3 in patient sperm, weakening the head-tail junction. |
Co-immunoprecipitation in HEK293T cells, immunofluorescence on patient sperm, whole-exome sequencing |
Molecular human reproduction |
Medium |
33848337
|
| 2022 |
SUN5 promotes colorectal cancer cell proliferation and migration by upregulating phosphorylated ERK1/2 (pERK1/2); this is mediated via Nesprin2 and involves SUN5 interaction with Nup93 to promote nuclear translocation of pERK1/2. |
Knockdown/overexpression in CRC cell lines, ERK inhibitor (PD0325901) rescue, xenograft transplantation, Co-IP with Nup93 |
Cancers |
Medium |
36358787
|
| 2023 |
ARRDC5 affects spermatogenesis by influencing the localization of SUN5 and NDC1; ARRDC5 likely acts through SEC22A-mediated vesicle trafficking to control transport and localization of SUN5 and other HTCA-related proteins responsible for sperm head-tail attachment. |
Arrdc5 knockout mouse, mass spectrometry, immunofluorescence |
Development (Cambridge, England) |
Medium |
37997706
|
| 2024 |
SUN5 interacts with LaminB1 (inner nuclear membrane) and with cytoskeletal GTPase Septin12 (and Septin2), forming a LaminB1/SUN5/Septin12 complex at the sperm neck. SUN5 connects the nucleus via LaminB1 and connects the proximal centriole via Septin12; SUN5-Septin12 binding promotes their co-aggregation at the sperm neck. Sun5 knockout disrupts Septin12-proximal centriole attachment to the nucleus, causing head-tail separation. |
Immunoprecipitation-mass spectrometry, Co-IP, immunofluorescence, Sun5 knockout mouse |
Molecular human reproduction |
High |
38870534
|
| 2024 |
SUN5 is involved in mRNA export in germ cells: in Sun5 KO mice, poly(A)+ RNA accumulates in nuclei of germ cells. SUN5 interacts with mRNA export factor Nxf1 and nucleoporin Nup93; loss of Sun5 reduces the Nxf1–Nup93 interaction and inhibits mRNA export through an Nxf1-dependent (not CRM1-dependent) pathway, contributing to abnormal spermatogenesis. |
Sun5 knockout mice, RNA interference in GC-2 cells, Co-IP of SUN5 with Nxf1 and Nup93, poly(A)+ RNA FISH, leptomycin B pharmacological block |
Acta biochimica et biophysica Sinica |
High |
39108207
|
| 2025 |
SUN5 interacts with TRIM28 to increase IκBα ubiquitination, activating the NF-κB signaling pathway; this leads to nuclear translocation of phosphorylated P65 and increased transcription of GLUT1 and LDHA, enhancing glycolysis in colorectal cancer cells. |
SUN5 overexpression/knockdown in CRC cells, Co-IP of SUN5 with TRIM28, IKK inhibitor (BAY11-7082), glucose uptake and lactate assays, xenograft transplantation |
Acta biochimica et biophysica Sinica |
Medium |
41311215
|
| 2026 |
By in situ cryo-electron tomography, SUN5 forms an extensive hexagonal lattice in the nuclear envelope at the base of the sperm head (confirmed in human, mouse, and boar sperm by superresolution fluorescence microscopy). This lattice maintains close apposition between inner and outer nuclear membranes; structural analysis supports a model in which LINC complexes form this lattice by laterally interacting at the outer nuclear membrane. |
Superresolution fluorescence microscopy, in situ cryo-electron tomography |
Proceedings of the National Academy of Sciences of the United States of America |
High |
41855266
|
| 2025 |
In-cell cryo-electron tomography of human spermatozoa reveals the sub-nanometer architecture of the trimeric ~130 kDa SUN5–Nesprin3 LINC complex forming a hexagonal lattice that stitches the nuclear envelope at the sperm base. A unique membrane-anchoring mechanism was identified: a SUN5 KASH-lid β-hairpin and a Nesprin3 amphipathic helix insert into the outer nuclear membrane, driving cooperative nuclear envelope remodeling and flattening of the caudal sperm nucleus. |
In-situ electron cryo-tomography, AlphaFold structural predictions, molecular dynamics simulations |
bioRxiv (preprint)preprint |
High |
bio_10.1101_2025.08.04.668116
|