Ask about this productRelated genes to: DNALI1 Blocking Peptide
- Gene:
- DNALI1 NIH gene
- Name:
- dynein axonemal light intermediate chain 1
- Previous symbol:
- -
- Synonyms:
- P28, hp28, dJ423B22.5
- Chromosome:
- 1p34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-06-12
- Date modifiied:
- 2016-10-05
Related products to: DNALI1 Blocking Peptide
Related articles to: DNALI1 Blocking Peptide
- The precise assembly of the sperm flagellum is essential for male fertility and has long been ascribed to kinesin-2-driven intraflagellar transport (IFT) of protein cargoes. However, during late spermiogenesis, when transcription activity is largely silenced, how the spatiotemporally regulated delivery of flagellar components remains poorly understood. Here, we systematically screened kinesin genes in asthenozoospermic patients and identified two homozygous deleterious KIF6 variants in unrelated men characterized by complete sperm immotility. Mouse models carrying the corresponding mutations recapitulated the human infertility phenotypes. Multi-omics analyses revealed that most testicular mRNAs remained largely unchanged in Kif6 mice, whereas proteins involved in axonemal organization and energy metabolism were markedly reduced. Mechanistically, KIF6 interacts with the RNA-binding proteins (RBPs) FMRP and FXR1 to assemble mRNP transport complexes that ferry transcripts encoding flagellar structural proteins (e.g., DNALI1) and metabolic enzymes (e.g., HK1). Impaired KIF6 function compromises mRNP trafficking to the developing flagellum, reducing flagellar transcript levels and ultimately causing decreased protein abundance and defective flagellar function. Collectively, we identify KIF6 as a key regulator of mRNA transport during spermiogenesis. It interacts with RBPs through a novel IFT-like pathway to deliver mRNAs essential for flagellar biogenesis, redefining the traditional protein-centric IFT paradigm. - Source: PubMed
Publication date: 2026/06/25
Xie ChunboYi SibingLin XinleZhang ShenWang WeiliYuan ShiminMeng LanlanLi YongTan ChenWei ChunjiaYu YanyanLiang YaoqiongZhang HuanHu LiangLu GuangxiuHe WenbinZhang QianjunDu JuanLin GeTu ChaofengTan Yue-Qiu - Severe asthenoteratozoospermia (ATZ) is a major cause of male infertility and is frequently associated with defects in sperm flagellar architecture. DNAH12 encodes a dynein heavy chain of the inner dynein arm (IDA); however, the spectrum of sperm structural abnormalities associated with DNAH12 mutations in humans remains incompletely characterized. - Source: PubMed
Publication date: 2026/06/19
Li GuotongLiu MeizhouZha XingXia XunYin ShikuiLi YuqianAtta SanaRaja AyllaXie QingsongZou SileGuo YudieWang CongyangHua RongCao YunxiaWu HuanLiu Yingchun - Primary human basal bronchial epithelial cells (HBECs) are an important population of progenitor cells capable of self-renewal and differentiation to maintain airway homeostasis. In air-liquid interface (ALI) culture, HBECs undergo mucociliary differentiation, providing a robust physiologic model to evaluate novel therapeutics such as in vitro-transcribed messenger RNA (IVT-mRNA). However, the impact of IVT-mRNA delivery on the differentiation potential of basal HBECs remains poorly characterised. Poly(beta amino) ester (PBAE) nanoparticles have demonstrated effective airway delivery of IVT-mRNA in various preclinical studies. Here, we aimed to understand the impact of PBAE-mediated mRNA transfection on basal HBEC differentiation at the ALI. We investigated IVT-mRNA encoding the ciliogenesis transcription factor Forkhead box J1 (FOXJ1) as a model tool for transient overexpression in primary basal HBECs and characterised its subsequent impact on epithelial integrity and differentiation at the ALI. PBAE-mediated delivery of FOXJ1 mRNA to submerged primary HBECs resulted in approximately 50% FOXJ1-positive cells and transient upregulation of key ciliogenesis-related genes, including DNALI1 and RSPH9. Following 28 days of differentiation at the ALI, FOXJ1- or reporter mRNA-transfected cultures displayed normal epithelial morphology, with tight junction and differentiation markers, proportions of secretory and ciliated cells, and ciliary ultrastructure comparable to those of non-transfected controls. These data indicate that PBAE-mediated IVT-mRNA delivery can transiently increase encoded protein expression in basal primary HBECs without impeding mucociliary differentiation. - Source: PubMed
Publication date: 2026/06/12
Konstantinidi RafaelaSubramanian MiraYates LauraLloyd Clare MSaglani SejalPatel Asha K - Primary ciliary dyskinesia (PCD) is a monogenic disorder of motile cilia characterized by impaired mucociliary clearance and multisystem involvement. We describe a patient with bronchiectasis, chronic rhinosinusitis, situs inversus, and primary infertility with hoard the splice-site variant (NM_015896.4:c.511-1G>A). High-speed video microscopy (HSVM) demonstrated near-complete immotility of respiratory cilia. RT-PCR and cDNA sequencing revealed aberrant splicing with insertion of a 100-bp fragment, leading to a frameshift and a pre-mature termination codon predicted to trigger non-sense-mediated mRNA decay and truncate the C-terminal MYND domain. Consistently, transcript and protein levels were markedly reduced. Transmission electron microscopy demonstrated loss of both outer and inner dynein arms. Concordantly, immunofluorescence showed absence of DNAH5, supporting an outer dynein arm defect. In addition, single-headed inner dynein arm components were selectively disrupted, as evidenced by loss of DNALI1, whereas the double-headed IDAf component DNAH2 was preserved. Notably, GAS8 (DRC4) was absent despite preserved DRC1 expression, suggesting that GAS8 loss in this case was not simply secondary to DRC1 deficiency and may reflect broader perturbation of nexin-dynein regulatory complex organization. Collectively, these findings expand the phenotypic spectrum and molecular characterization of ZMYND10-related PCD and provide further insight into dynein arm assembly and axonemal organization. - Source: PubMed
Publication date: 2026/05/08
He JieLu XiangyangGuo ManqingYang BinyiZhou XianglinLiu YingFan HuiYang DanhuiLuo Hong - Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous disorder leading to destructive airway disease with severe bronchiectasis and chronic lung failure in adulthood. Pathogenic variants in CCDC40 are associated with more severe reduction of lung function compared to most other PCD types. Currently, no therapies correcting the underlying disease mechanism are available. Here we investigate the efficacy of lipidoid nanoparticle-formulated mRNA encoding human CCDC40 (LNP-CCDC40-mRNA) as a corrective measure for structural and functional defects in vitro (human cells) and in vivo (zebrafish). Human nasal respiratory epithelial cells cultured at air-liquid-interface from five CCDC40-deficient individuals and a newly generated vertebrate animal model (ccdc40-/- zebrafish) were treated with LNP-CCDC40-mRNA. CCDC40-deficient cells were analyzed by high-speed video microscopy and immunofluorescence microscopy. ccdc40-/- zebrafish olfactory pit cilia were analyzed by high-speed video microscopy and fluid flow assays. Topical application of exogenous LNP-CCDC40-mRNA to CCDC40-deficient cells results in endogenous CCDC40 expression (10-74% of ciliated cells), enabling axonemal integration of CCDC40-associated proteins (CCDC39, GAS8/DRC4, DNALI1). Consistently, ciliary beat frequencies were significantly increased in treated CCDC40-deficient cells and comparable to healthy control cells. Further, we showed improved ciliary transport of fluorescent particles. Injection or topical application of human LNP-CCDC40-mRNA to ccdc40-/- zebrafish significantly increased ciliary motility and established directional flow in olfactory pits. We provide structural and functional evidence in vitro and in vivo for the biological efficacy of LNP-CCDC40-mRNA in CCDC40-deficient respiratory cells and zebrafish. Based on our results, an in vivo human study (Phase 1 trial) is planned in individuals with pathogenic variants in CCDC40. - Source: PubMed
Publication date: 2026/03/30
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