For instance, LRRC4 is not present during the early (embryonic) development of the mouse brain.

As a consequence, the deletion of the LRRC4 gene adversely affects synaptic plasticity (i.e., the ability of neuronal synapses to remodel as necessary) and memory formation in the hippocampus.Įxperiments conducted on laboratory mice reveal interesting facts. LRRC4/NGL2 is highly expressed in multiple key brain regions and also supports memory formation in the hippocampus. Quite interestingly, LRRC4-also known by the name 'netrin-G ligand 2 (or NGL2)'-has been shown to interact with the protein netrinG2, which controls the formation of neuronal circuits and synapses, even in the brain. After receiving information from the cerebral cortex, the hippocampus processes information, then forms a memory, and stores it with the help of neuronal synapses. The hippocampus, for example, is the memory center of the brain-it coordinates learning and memory performance. Our brain functions in a complex way, with each region performing a specific role. Minghua Wu from Central South University, China, says, 'In this review, we mainly discuss the effects of LRRC4 on memory by promoting the formation of excitatory synapses and long-term potentiation (LTP), the effects of LRRC4 mutation on psychoneurosis, and the new mechanism of LRRC4 in GB genesis and progression.' In a review article published in the Chinese Medical Journal, researchers shed light on the key physiological mechanisms regulated by this gene, and the effects of its mutation. Leucine-rich repeats containing 4 (LRRC4)-a gene abundantly found in the brain and located on human chromosome 7q31–32-plays a pivotal role in memory formation, autism, spinal cord injury, as well as in determining the malignant potential, development, and progression of glioblastoma (GB), an aggressive cancer involving the brain and/or spinal cord. CCL2: Chemokine (C-C motif) ligand 2 Circ-CD44: CircRNA-CD44 CU元: Cullin-3 DEPTOR: DEP domain containing mTOR interacting protein DNMT3A: DNA methyltransferase 3A EED: Embryonic ectoderm development EGF: Epidermal growth factor EGFR: Epidermal growth factor receptor eIF4A3: Eukaryotic initiation factor 4A3 ERK: Extracellular-signal-regulated kinases EZH2: Enhancer of zeste homolog 2 HSP90: Heat shock protein 90 IFN-γ: Interferon-γ IL-6: Interleukin 6 IκB-α: Inhibitor of NF-κB IKKβ: Inhibitor of NF-κB kinase subunit beta LRRC4: Leucine-rich repeats containing 4 MEK1/2: Mitogen-activated protein kinase kinase 1/2 miR: MicroRNA miRNA: MicroRNA mRNA: Messenger RNA mTOR: Mammalian target of rapamycin NF-κB: Nuclear factor-κB P: Phosphorylation PDPK1: 3-Phosphoinositide dependent protein kinase 1 pre-mRNA: Pre-messenger RNA SAM68: Signal transduction associated protein 68 SMAD6: Mothers against decapentaplegic homolog 6 Teff: Effector T cell TF: Transcription factor Treg: Regulatory T cell ULK1: Unc-51 like autophagy activating kinase 1.

LRRC4 binds to Sam68 to form a complex, which prevents Sam68 from binding to CD44 pre-mRNA, and promotes the binding between eIF4a3 and CD44 pre-mRNA, thereby promoting the formation of circCD44. LRRC4 directly interacts with PDPK1 and HSP90 to phosphorylate IKKβSer181, resulting in activating the NF-κB signaling pathway to facilitate cytokine secretion, thereby reprogramming the glioma immune microenvironment. LRRC4 and MEK1/2 competitively bind to ERK1/2, thereby blocking ERK1/2 entry into the nucleus, and inhibiting the transcription of downstream genes. The interaction between LRRC4 and DEPTOR promoted the ubiquitination modification and degradation of DEPTOR, which leads to the phosphorylation of mTOR protein, resulting in inhibiting the activity of downstream protein ULK1, and then inhibiting the occurrence of autophagy. miRNA-101 reverses the hypermethylation modification of the promoter region of LRRC4 by targeting EZH2, EED, and DNMT3a, thereby restoring the expression of LRRC4 in glioma cells. Recent research progress of LRRC4 in glioma.

Mouse brain xsection