| 2012 |
KASH5 is a germ cell-specific protein that localizes exclusively at telomeres from leptotene to diplotene stages in spermatocytes and oocytes, contains KASH-related sequences that directly interact with SUN1, and mediates telomere localization at the nuclear envelope. |
Subcellular localization screening in mouse spermatocytes, co-immunoprecipitation, direct protein interaction assays |
The Journal of cell biology |
High |
22826121
|
| 2012 |
KASH5 interacts with the microtubule-associated dynein-dynactin complex, connecting the telomere-associated SUN1 protein to the cytoplasmic force-generating machinery for meiotic chromosome movement. |
Co-immunoprecipitation of dynein-dynactin with KASH5 in mouse spermatocytes |
The Journal of cell biology |
High |
22826121
|
| 2013 |
KASH5 is a dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with SUN1; mice deficient in KASH5 are infertile with meiotic arrest in which pairing of homologous chromosomes fails, demonstrating that telomere attachment to the NE alone is insufficient and that coupling to cytoplasmic dynein is required. |
Genetic knockout mouse model (KASH5-deficient mice), immunofluorescence, chromosome spread analysis |
The Journal of cell biology |
High |
24062341
|
| 2015 |
Quantitative 4D fluorescence imaging confirmed that SUN1/KASH5, microtubules, and dynein—but not actin—are necessary for rapid prophase movements (RPMs) of meiotic chromosomes; KASH5 loss results in loss of both nuclear rotation and individual chromosome telomere movements along microtubule tracks. |
4D fluorescence imaging in mouse seminiferous tubules, quantitative motion analysis, pharmacological inhibition and genetic depletion |
Cell reports |
High |
25892231
|
| 2014 |
CDK2 ablation causes abnormal cap-like nuclear envelope distribution of KASH5 (and SUN1 and lamin C2) facing the centrosome in spermatocytes; CDK2 phosphorylates SUN1 in vitro, and some telomeres detach from the NE and associate with NE-detached vesicles containing SUN1, indicating CDK2 governs NE structure required for proper KASH5/SUN1 function. |
Immunofluorescence, electron microscopy, in vitro kinase assay with mouse testis CDK2 |
Journal of cell science |
Medium |
25380821
|
| 2016 |
KASH5 depletion in mouse oocytes arrests most oocytes at the germinal vesicle (GV) stage, causes small and abnormal spindles after GVBD, reduces cytoplasmic F-actin mesh, and displaces pericentrin and P150(Glued); SUN1 depletion causes KASH5 to relocalize exclusively near the oocyte cortex, but KASH5 depletion does not affect SUN1 localization, establishing a directional dependency. |
Gene silencing (siRNA/morpholino), immunofluorescence, live imaging in mouse oocytes |
Scientific reports |
Medium |
26842404
|
| 2020 |
Crystal structures of human SUN2 in complex with the KASH5 peptide reveal that the KASH5 peptide adopts a distinct conformation compared to Nesprin1/2 KASH peptides when bound to SUN2, while sharing core interactions at the C-terminal KASH residues; differences include the KASH-lid and cation loop interactions. |
X-ray crystallography of SUN2-KASH5 peptide complex |
Journal of molecular biology |
High |
33058875
|
| 2021 |
Crystallographic and biophysical evidence shows that SUN-KASH forms a constitutive 6:6 complex (two head-to-head 3:3 trimers), providing a molecular mechanism for branched LINC complex networks; KASH5 participates in this higher-order assembly. Zinc coordination by Nesprin-4 was identified as one distinct mechanism, with KASH5 using a structurally diverse mode to achieve the same 6:6 topology. |
X-ray crystallography, biophysical assays (SEC, ITC), structural analysis of SUN-KASH complexes |
eLife |
High |
33393904
|
| 2021 |
A human infertility-associated KASH5 variant (L535Q) within the transmembrane domain reduces hydrophobicity and misdirects KASH5 from the ER/outer nuclear membrane to the mitochondrial membrane, accounting for the infertility phenotype; amino acid substitution studies mapped the hydrophobicity requirement for ER/ONM targeting. |
Site-directed mutagenesis, subcellular fractionation, fluorescence microscopy in cultured cells, hydrophobicity calculations |
Scientific reports |
Medium |
33980926
|
| 2022 |
KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor in vitro; mutations in the dynein-binding surface of KASH5 abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. |
In vitro reconstitution of dynein motility (single-molecule TIRF), pulldown assays, mutagenesis, immunofluorescence in spermatocytes |
eLife |
High |
35703493
|
| 2022 |
A homozygous missense mutation in CCDC155/KASH5 (p.Leu197Pro) in the conserved CC domain blocks nuclear envelope distribution of KASH5 and prevents NE-specific enrichment of SUN1, causing meiotic arrest and infertility in humans (NOA and POI); the mutation was validated ex vivo and in vitro. |
Whole-exome sequencing, functional studies in patient-derived cells (ex vivo/in vitro localization assays), histological analysis |
Human genetics |
Medium |
35587281
|
| 2022 |
A homozygous splicing variant in KASH5 (c.747G>A) disturbs nuclear membrane localization of KASH5 and its binding with SUN1; Kash5 C-terminal deleted mice show defective meiotic homolog pairing and accelerated oocyte depletion, establishing that the KASH5 C-terminus and SUN1 interaction are essential for meiotic prophase I and ovarian reserve maintenance. |
Whole-exome sequencing, in vitro functional studies, mouse model (Kash5 C-terminal deletion), histology, oocyte spreads |
The Journal of clinical endocrinology and metabolism |
Medium |
35708642
|
| 2023 |
KASH5 promotes dynein motility in vitro as an activating adaptor; KASH5 interacts with dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal domain; KASH5 N-terminal EF-hand calcium-binding residues are essential for dynein interaction (mutation of key Ca2+-binding residues disrupts this); dynein can be recruited to KASH5 at the NE independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5-dynein complex; cytosolic KASH5 inhibits dynein's interphase functions. |
In vitro dynein motility assays, Co-IP, mutagenesis of EF-hand residues, dominant-negative overexpression in cultured cells |
The Journal of cell biology |
High |
36946995
|
| 2023 |
A homozygous KASH5 frameshift mutation (c.1270_1273del, p.Arg424Thrfs*20) causes absence of KASH5 protein in testes and NOA with meiotic arrest before pachytene; truncated KASH5 protein encircles the nucleus similarly to wild-type but shows weakened interaction with SUN1, explaining the meiotic defect. |
Whole-exome sequencing, immunofluorescence in testes, co-immunoprecipitation of truncated vs. full-length KASH5 with SUN1 in cultured cells |
Frontiers in endocrinology |
Medium |
36864840
|
| 2023 |
Loss of SUN1 function in human spermatocytes significantly reduces KASH5 levels at the inner nuclear membrane and disrupts chromosomal telomere attachment, establishing that SUN1 is required for KASH5 enrichment at the NE in a human disease context. |
Whole-exome sequencing, immunofluorescence of patient spermatocytes |
Human genetics |
Low |
36933034
|
| 2025 |
KIF5B (a kinesin) directly interacts with KASH5 via KASH5's N-terminal EF-hand domains, as shown by co-immunoprecipitation, yeast two-hybrid with KASH5 as bait, TIRF microscopy, and microtubule sedimentation with purified recombinant proteins; KIF5B is recruited by KASH5-SUN1 to the nuclear envelope and colocalizes with KASH5 at telomeres in spermatocytes; chemical inhibition of KIF5B reduces telomere-led chromosome RPMs. |
Co-immunoprecipitation, yeast two-hybrid, TIRF microscopy with purified proteins, microtubule sedimentation assay, pharmacological inhibition, immunofluorescence in spermatocytes |
bioRxivpreprint |
Medium |
40501626
|