Ask about this productRelated genes to: ELFN2 antibody
- Gene:
- ELFN2 NIH gene
- Name:
- extracellular leucine rich repeat and fibronectin type III domain containing 2
- Previous symbol:
- LRRC62, PPP1R29
- Synonyms:
- dJ63G5.3, KIAA1904
- Chromosome:
- 22q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-10-16
- Date modifiied:
- 2016-06-06
Related products to: ELFN2 antibody
Related articles to: ELFN2 antibody
- The metabotropic glutamate receptor 6 (mGluR6), encoded by , is a core component of the ON-bipolar signaling cascade in the retina, but its role in human retinal development remains unclear. Here, we used temporally controlled CRISPR-based genetic ablation in human induced pluripotent stem cell-derived retinal organoids to define the developmental functions of mGluR6. Unexpectedly, we found that mGluR6 is expressed not only in depolarizing ON-bipolar cells but also transiently in cone photoreceptors during human retinal development, a pattern not observed in the mouse retina. Early loss of prior to synaptogenesis disrupted cone pedicle architecture, leading to mislocalization of synaptic proteins including Bassoon, ELFN2, and TRPM1, and ultimately resulting in widening or duplication of the outer plexiform layer (OPL). In contrast, deletion after synapse formation did not alter OPL synapses or morphology, revealing a temporally restricted requirement for mGluR6 during circuit assembly. These findings uncover a previously unrecognized role for mGluR6 in coordinating cone terminal targeting and synaptic layer assembly during human retinal development and highlight the power of temporally controlled genetic manipulation in organoid systems to reveal species-specific mechanisms of neural circuit formation. - Source: PubMed
Publication date: 2026/04/27
Bahmani LeilaGalvan PatriciaHosseini HiradBai JinlunBharathan Sumitha PChen MichaelStepanian KaylaThornton Matthew EGrubbs Brendan HNagiel Aaron - Lymph node metastasis (LNM) is the most frequent metastatic pathway in gastric cancer (GC) and a major determinant of poor prognosis, but the underlying molecular mechanisms remain poorly defined. In this study, we investigated the role of extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2 (ELFN2) in LNM and its therapeutic potential in GC. ELFN2 expression was examined in clinical GC tissues and found to be significantly downregulated in cases with LNM, with low ELFN2 levels correlating with unfavorable patient survival. Mechanistic studies demonstrated that ELFN2 interacts directly with the catalytic subunit alpha of protein phosphatase-1 (PP1A), thereby inhibiting YAP dephosphorylation at Ser127. This regulation promotes YAP nuclear export and functional inactivation. Pharmacological inhibition of PP1A abrogated ELFN2-induced YAP inactivation, confirming the requirement of PP1A in this process. To further validate the biological significance of ELFN2, we established in vivo models of LNM and peritoneal carcinomatosis, which consistently showed that ELFN2 suppresses metastatic dissemination. Together, our results reveal a novel ELFN2/PP1A/YAP signaling axis that plays a critical role in controlling LNM in GC. Importantly, these findings not only provide new insights into the molecular mechanisms governing GC metastasis but also highlight ELFN2 as a promising biomarker and potential therapeutic target for the management of GC patients at high risk of LNM. - Source: PubMed
Publication date: 2026/04/10
Ling RuoyuYang HuaZhang GuofanChen JingYe ZhaoGou LongfeiLei XuetaoYang QingbinPeng YanmeiYe GengtaiLi GuoxinChen Hao - The group III metabotropic glutamate receptors (mGlu receptors) are predominantly expressed presynaptically throughout the central nervous system (CNS) where they regulate the release of glutamate and GABA. These receptors have recently been shown to be anchored by transsynaptic expression of the laminin proteins ELFN1 and ELFN2. In particular, the mGlu receptor is localized at presynaptic active zones from pyramidal cells to somatostatin-containing interneurons with postsynaptic ELFN1, and this interaction drives the rapidly facilitating nature of these synapses in the hippocampus and cortex. Interestingly, individuals with mutations in or genes present with attention-deficit hyperactivity disorder and epilepsy, and knockout mice of each of these proteins develop seizures with very similar time courses. In the current manuscript, we explore the hypothesis that the pharmacology of positive and negative allosteric modulators (PAMs and NAMs) of mGlu might be changed in the presence of ELFN1. These results showed that, across a range of NAMs, we observed similar efficacy in the presence of ELFN1. For PAMs, we observed decreased maximal potentiation when ELFN1 was present, but all examined compounds were still able to potentiate receptor signaling regardless of ELFN1 expression. Finally, we confirm that a tool PAM with mGlu activity is able to potentiate responses at pyramidal cell-somatostatin interneuron synapses where ELFN1 is expressed. These results suggest that, for the modulators shown here, native tissue activity should be retained in the presence of ELFN1 expression. - Source: PubMed
Publication date: 2025/07/21
Lei XiaXiang ZixiuRodriguez Alice LWilson Margaret LNiswender Colleen M - Synaptic adhesion molecules are essential components of the synapse, yet the diversity of these molecules and their associated functions remain to be fully characterized. Extracellular leucine rich repeat and fibronectin type III domain containing 1 (ELFN1) is a postsynaptic adhesion molecule in the brain that has been increasingly implicated in human neurological disease. ELFN1 is best known for trans-synaptically modulating group III metabotropic glutamate receptors (mGluRs). However, little is known about ELFN1 organization and regulation, which likely govern and precede its ultimate trans-synaptic engagement with group III mGluRs. Herein, we report that the intracellular ELFN1 domain controls membrane trafficking and post-synaptic localization of ELFN1. We pinpoint a ∼30 amino acid juxtamembranous region required for membrane-targeting and discover that ELFN1 exists as an obligate homodimer prior to its trafficking to the membrane. We determine that ELFN1 homodimerization is not appreciably affected by the intracellular region and instead utilizes the extracellular leucine rich repeats (LRR) domain. We find that a single membrane-targeting motif located in one protomer is sufficient for effective trafficking of the ELFN1 homodimer. We further demonstrate that the closest ELFN1 homolog, synaptic adhesion molecule ELFN2, exhibits similar properties and participates in heterodimerization with ELFN1. This establishes distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, post-synaptic localization, and dimerization while indicating conservation of the mechanisms across the ELFN subfamily of cell adhesion molecules. - Source: PubMed
Publication date: 2024/12/13
Dunn Henry ADhaliwal Simran KChang Chu-TingMartemyanov Kirill A - Synaptic transmission from retinal photoreceptors to downstream ON-type bipolar cells (BCs) depends on the postsynaptic metabotropic glutamate receptor mGluR6, located at the BC dendritic tips. Glutamate binding to mGluR6 initiates G-protein signaling that ultimately leads to BC depolarization in response to light. The mGluR6 receptor also engages in trans-synaptic interactions with presynaptic ELFN adhesion proteins. The roles of post-translational modifications in mGluR6 trafficking and function are unknown. Treatment with glycosidase enzymes PNGase F and Endo H demonstrated that both endogenous and heterologously expressed mGluR6 contain complex N-glycosylation acquired in the Golgi. Pull-down experiments with ELFN1 and ELFN2 extracellular domains revealed that these proteins interact exclusively with the complex glycosylated form of mGluR6. Mutation of the four predicted N-glycosylation sites, either singly or in combination, revealed that all four sites are glycosylated. Single mutations partially reduced, but did not abolish, surface expression in heterologous cells, while triple mutants had little or no surface expression, indicating that no single glycosylation site is necessary or sufficient for plasma membrane trafficking. Mutation at N445 severely impaired both ELFN1 and ELFN2 binding. All single mutants exhibited dendritic tip enrichment in rod BCs, as did the triple mutant with N445 as the sole N-glycosylation site, demonstrating that glycosylation at N445 is sufficient but not necessary for dendritic tip localization. The quadruple mutant was completely mislocalized. These results reveal a key role for complex N-glycosylation in regulating mGluR6 trafficking and ELFN binding, and by extension, function of the photoreceptor synapses. - Source: PubMed
Publication date: 2024/02/28
Miller Michael LPindwarawala MustansirAgosto Melina A