Ask about this productRelated genes to: UNC84A antibody
- Gene:
- SUN1 NIH gene
- Name:
- Sad1 and UNC84 domain containing 1
- Previous symbol:
- UNC84A
- Synonyms:
- KIAA0810, FLJ12407
- Chromosome:
- 7p22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-09-13
- Date modifiied:
- 2014-11-18
Related products to: UNC84A antibody
Related articles to: UNC84A antibody
- SUN1/2, core components of the linker of nucleoskeleton and cytoskeleton complex, transmit extracellular mechanical forces to nuclear lamina and chromatin. However, their role in regulating peripheral chromatin in mechanosensing and mechanoadaptation remains unclear. Using CRISPR/Cas9-mediated knockout of or in myoblasts, we identified a SUN1/2-dependent mechano-feedback loop. SUN1/2 depletion down-regulates genes for cell adhesion (e.g., integrin alpha-4) and for mechanotransduction (e.g., cell division cycle 42 and Ras homolog family member A). The primary mechanism involves redistribution of heterochromatin from nuclear periphery to the nucleoplasm and remodeling of lamina-associated domains (LADs), as an adaptive response to the loss of SUN proteins. Furthermore, lamin A/C acts as a key downstream effector, consistently modulating adhesion-related gene expression through the remodeling of LADs. Functionally, knockout of either or aggravates differentiation defects in C2C12 myoblasts and abolishes adaptive responses to mechanical cues. This study provides proof of concept that nuclear mechanotransduction proteins can modulate cellular mechanoadaptation via a mechano-feedback loop, which coordinates LAD reorganization with the expression of upstream mechanotransduction genes. - Source: PubMed
Publication date: 2026/05/14
Xie YafanZuo ZhaoyanLu ChenfeiZhao YanjingGuo LipingXu WeiLiu FuhaiGuidoin RobertZhang HaoyueQiu JuhuiWang GuixuePeng Qin - During myogenic differentiation, the Microtubule-Organizing Center (MTOC) is relocated to the nuclear envelope by a molecular platform including Linker of Nucleoskeleton and Cytoskeleton (LINC) complex proteins, A Kinase Anchoring Proteins (AKAP9 and AKAP6) and Pericentriolar Material 1 (PCM-1). Here, we show that emerin is required for centrosomal protein recruitment to the nuclear periphery of myonuclei and microtubule dynamics. In fact, in type 1 Emery-Dreifuss Muscular Dystrophy (EDMD1), loss of emerin was associated with altered pericentrin recruitment to the nuclear envelope, LINC protein impairment at the nuclear poles of myonuclei and microtubule organization defects. As a consequence, dynein, mitochondrial distribution and nuclear alignment along the longitudinal axis of the myotubes were altered in EDMD1 myotubes. Moreover, reduced levels of AKAP6 and PKA were detected at the nuclear periphery of EDMD1 myotubes, possibly contributing to an aberrant nuclear localization of the mechanosensing factor YAP. Upon rescue of emerin expression by CRISPR correction of mutated EMD gene: SUN1/2, pericentrin, AKAP6 and PKA were restored at the nuclear envelope and a correct YAP localization was observed in EDMD1 muscle cells. These results show that emerin is required for Nuclear Envelope-MTOC (NE-MTOC) organization in differentiating skeletal muscle cells and suggest that disruption of such complex is a key pathogenetic event in Emery-Dreifuss Muscular Dystrophy. - Source: PubMed
Publication date: 2026/05/12
Mattioli ElisabettaCenni VittoriaSabatelli PatriziaSchena ElisaSanti SpartacoFiorillo ChiaraBruno ClaudioPini AntonellaGiannotta MelaniaCavallo MarcoErrani CostantinoCattin EleonoraBenati DanielaRecchia AlessandraLattanzi Giovanna - Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease and strongly linked to obesity and insulin resistance. We previously reported that the common nuclear envelope variant rs6461378 (g.842031C>T; H118Y) associated with MASLD and related traits including insulin resistance. To gain insight into how wild-type (WT) and H118Y SUN1 might differentially impact insulin signaling, we performed affinity purification-mass spectrometry (AP-MS) in human liver-derived cells stably expressing WT or H118Y SUN1. Unbiased AP-MS revealed a novel SUN1-CUL3 interaction, with comparative analysis showing that WT SUN1 interacted robustly with CUL3, while CUL3 interaction was markedly diminished with H118Y SUN1. Cells in which was silenced via siRNA, or in which H118Y SUN1 was ectopically expressed, showed increased CUL3 neddylation, which is required for cullin RING ligase (CRL)-mediated ubiquitination of insulin receptor substrate (IRS) proteins. Inhibition of neddylation restored IRS-1 levels and insulin signaling in H118Y SUN1-expressing cells. Together, our findings provide a potential mechanism of H118Y SUN1-driven insulin resistance and a viable therapeutic approach for its reversal. - Source: PubMed
Publication date: 2026/04/20
Upadhyay Kapil KYang YunshuShah ArenBasrur VenkateshaNesvizhskii Alexey IBrady Graham F - Many DNA viruses including polyomaviruses (PyVs) enter the host nucleus to cause infection, although how this is accomplished is unclear. To infect cells, the prototype PyV SV40 targets to the Nesprin-2 outer nuclear membrane protein and enters the nucleus via the nuclear pore complex (NPC). Host factors that function with Nesprin-2 to target SV40 to the nuclear membrane and drive NPC-dependent nuclear entry are unknown. Here we demonstrate that the SUN1 inner nuclear membrane protein acts coordinately with its binding-partner Nesprin-2 to target cytosol-localized SV40 to the nuclear membrane. Strikingly, despite localizing to the perinuclear space, the SUN domain of SUN1 plays a crucial role in Nesprin-2-dependent recruitment of cytosolic SV40. After targeting, SV40 binds to the NPC-associated importin receptor KPNA4, which translocates the virus into the nucleus. Our results reveal how a DNA virus exploits the Nesprin-2-SUN1-KPNA4 axis for stepwise targeting and entry into the nucleus to cause infection. - Source: PubMed
Publication date: 2026/03/15
Gohmann LukeTsai Billy - Nuclear movement and positioning can be mediated by linker of nucleoskeleton and cytoskeleton (LINC) complexes, which consist of Sad1-UNC-84 (SUN) proteins and Klarsicht-ANC-1-Syne homology (KASH) proteins. KASH proteins bind SUN proteins via a short KASH domain. Unlike animal KASH domains, plant KASH domains are shorter, lack ability to form disulfide bonds and have a different C-terminal sequence motif. Here, we examined the specificity of KASH domains using two Arabidopsis KASH proteins, WIP1 and SINE1. We show experimentally that the SINE1 KASH domain is required for SINE1 function in stomata and the WIP1 KASH domain for WIP1 function in root hairs, but that the SINE1 and WIP1 KASH domains are interchangeable for the WIP1 role in nuclear movement in pollen tubes. Through molecular modeling, we found that SINE1 has two distinct binding modes that are dependent on its interaction partner (SUN1 or SUN2), whereas WIP1 binds very similarly to both SUN1 and SUN2. We propose that this requirement for specific KASH domains reflects differences between the SUN1-SINE1 and SUN1-WIP1 interaction models and might indicate a different tolerance of the interactions to force. - Source: PubMed
Publication date: 2026/04/30
Schumacher Lily AGroves Norman RConway Daniel EMeier Iris