ArticleNature communications2023
A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex.Nature communications · 2026Article
- Deciphering the functions of NELL2 in tumorigenesis and beyond.Frontiers in immunology · 2026Review
- Mapping cis- and trans-regulatory target genes of human-specific deletions.Nature communications · 2025Article
- Transcriptomic analysis reveals liver lncRNA-mRNA regulatory networks mediating Nicol1-induced growth and reproduction in golden pompano (Trachinotus ovatus).BMC genomics · 2025Article
- Ewing sarcoma depends on C4orf48/NICOL, a NELL2 cofactor regulated by Hippo signaling.Cellular signalling · 2025Article
- Inhibition of ROS1 activity with lorlatinib reversibly suppresses fertility in male mice.Andrology · 2025Article
- Testis expressed 50 is essential for maintaining sperm acrosome integrity during epididymal transit.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chemical Synthesis of NICOL, A Coligand Secreted Protein Mediating Mammalian Male Reproductive Tract Trans-luminal Signaling.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- CRISPR/Cas9-mediated genome editing reveals seven testis-enriched transmembrane glycoproteins dispensable for male fertility in mice.Andrology · 2025Article
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
- Structures and pH-dependent dimerization of the sevenless receptor tyrosine kinase.Molecular cell · 2024Article
- Eighteen genes primarily expressed in the testis are not required for male fertility in mice†.Biology of reproduction · 2024Article
- The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.The Journal of clinical investigation · 2024Article
- Distinct actions of testicular endocrine and lumicrine signaling on the proximal epididymal transcriptome.Reproductive biology and endocrinology : RB&E · 2024Article
- Busulfan administration replicated the characteristics of the epididymal initial segment observed in mice lacking testis-epididymis lumicrine signaling.The Journal of reproduction and development · 2024Article
- Expression of NELL2/NICOL-ROS1 lumicrine signaling-related molecules in the human male reproductive tract.Reproductive biology and endocrinology : RB&E · 2024Article
- Gene-deficient mouse model established by CRISPR/Cas9 system reveals 15 reproductive organ-enriched genes dispensable for male fertility.Frontiers in cell and developmental biology · 2024Article
- Lumicrine signaling: Extracellular regulation of sperm maturation in the male reproductive tract lumen.Genes to cells : devoted to molecular & cellular mechanisms · 2023Review
- Adhesion G protein-coupled receptor G2 is dispensable for lumicrine signaling regulating epididymal initial segment differentiation and gene expression†.Biology of reproduction · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the epididymis. Males lacking Nicol are sterile due to impaired NELL2-mediated lumicrine signalling, leading to defective epididymal differentiation and deficient sperm maturation but can be restored by NICOL expression in testicular germ cells. Our results demonstrate how lumicrine signalling regulates epididymal function for successful sperm maturation and male fertility.
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Registered trials
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