DLG1

Last update 08 May 2025

Basic Info

Synonyms

discs large MAGUK scaffold protein 1, Disks large homolog 1, dJ1061C18.1.1

+ [6]

Introduction

Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). May also play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497).

100 Clinical Results associated with DLG1

100 Translational Medicine associated with DLG1

0 Patents (Medical) associated with DLG1

682

Literatures (Medical) associated with DLG1

06 Apr 2025·Japanese Journal of Clinical Oncology

Familial adenomatous polyposis family with clustering of psychiatric disorders

Article

Author: Mishima, Kazuo ; Taguchi, Daiki ; Shibata, Hiroyuki ; Kodama, Naoaki ; Nanjo, Hiroshi ; Takahashi, Tsutomu ; Shimazu, Kazuhiro ; Yoshida, Taichi ; Shinozaki, Hanae ; Fukuda, Koji ; Noutomi, Rie ; Ishikawa, Hayahito ; Noguchi, Atsuko ; Funaki, Masako

AbstractFamilial adenomatous polyposis (FAP) is an inherited disorder that follows an autosomal dominant inheritance pattern and is caused by a germline pathogenic variant in the APC gene. FAP also has extracolonic manifestations, including osteomas, brain tumors, and congenital hypertrophy of the retinal pigmented epithelium. Desmoid tumor is a rare soft-tissue tumor often associated with FAP. APC is a WNT signal transduction molecule that is abundantly expressed in the central nervous system. The truncation mutations of the APC gene are responsible for FAP. Further, the C-terminal domains of APC associate with proteins such as EB1 and hDLG, which are involved in central nervous system functions. In recent years, several reports have indicated an association between FAP and mental disorders. We have identified a family with FAP that has a cluster of mental disorders. The female probrand experienced FAP and desmoid tumors in her thirties. She underwent a total colectomy and tumor resection. Her genetic test revealed a pathogenic germline pathogenic variant in the APC gene, c.3183_3187del. Her maternal grandmother and great-grandmother had colorectal polyposis. She has some mental disorders, and her son and daughter both have autism spectrum disorder (ASD). It was reported that her younger sister and her two daughters have intellectual disability and symptoms of ASD. For these situations, we found that mental health care is crucial when providing genetic counseling and medical care, especially to younger patients with FAP and carriers of pathological variants of the APC gene.

01 Apr 2025·Esophagus

Circ_DLG1 facilitates cell proliferation and metastasis of esophageal squamous cell carcinoma via upregulating MAP3K9

Article

Author: Hu, Hongxia ; Wu, Yafan ; Gou, Yunjiu ; Yang, Yi ; Wang, Huilin ; Pang, Yao

BACKGROUNDCirc_DLG1 is found to be aberrantly expressed in esophageal squamous cell carcinoma (ESCC) tissues, but its role in the progression of ESCC remains to be elucidated.METHODSThe expression of circ_DLG1, miR-338-3p and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was measured by qRT-PCR. Cell cycle, viability, migration and invasion were investigated using flow cytometry, MTT assay and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2 (ERKs), phosphor ERKs (p-ERKs) were detected by western blot. Dual-luciferase reporter assay and RIP assay were performed to verify the putative relationship between miR-338-3p and circ_DLG1 or MAP3K9. Animal experiments were performed to ascertain the role of circ_DLG1 in vivo.RESULTSCirc_DLG1 expression was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC, and its overexpression rescued the effects of circ_DLG1 knockdown on cell proliferation and metastasis. Besides, circ_DLG1 positively regulated MAP3K9 expression by competitively targeting miR-338-3p. Also, miR-338-3p inhibition or MAP3K9 overexpression recovered the inhibiting effect of circ_DLG1 knockdown on the phosphorylated levels of p38 and ERKs. In addition, circ_DLG1 knockdown blocked the tumor growth in vivo by regulating the miR-338-3p/MAP3K9 axis.CONCLUSIONCirc_DLG1 promoted malignant progression of ESCC by mediating the miR-338-3p/MAP3K9/p38/ERK pathway, indicating that targeted inhibition of the circ_DLG1/miR-338-3p/MAP3K9/p38/ERK axis might be an effective strategy for the treatment of ESCC.

14 Mar 2025·Schizophrenia Bulletin

Dysregulated Transcript Expression but Not Function of the Glutamate Transporter EAAT2 in the Dorsolateral Prefrontal Cortex in Schizophrenia

Article

Author: Shan, Dan ; McCullumsmith, Robert E ; Choi, Jae Hyuk ; O’Donovan, Sinead M ; Wu, Xiaojun

AbstractBackgroundSchizophrenia (SCZ) is a serious mental illness with complex pathology, including abnormalities in the glutamate system. Glutamate is rapidly removed from the synapse by excitatory amino acid transporters (EAATs). Changes in the expression and localization of the primary glutamate transporter EAAT2 are found in the brain in central nervous system (CNS) disorders including SCZ. We hypothesize that neuronal expression and function of EAAT2 are increased in the frontal cortex in subjects diagnosed with SCZ.Study DesignEAAT2 protein expression and glutamate transporter function were assayed in synaptosome preparations from the dorsolateral prefrontal cortex (DLPFC) of SCZ subjects and age- and sex-matched nonpsychiatrically ill controls. EAAT2 splice variant transcript expression was assayed in enriched populations of neurons and astrocytes from the DLPFC. Pathway analysis of publicly available transcriptomic datasets was carried out to identify biological changes associated with EAAT2 perturbation in different cell types.ResultsWe found no significant changes in EAAT2 protein expression or glutamate uptake in the DLPFC in SCZ subjects compared with controls (n = 10/group). Transcript expression of EAAT2 and signaling molecules associated with EAAT2b trafficking (CaMKIIa and DLG1) were significantly altered in enriched populations of astrocytes and pyramidal neurons (P < .05) in SCZ (n = 16/group). These changes were not associated with antipsychotic medications. Pathway analysis also identified cell-type-specific enrichment of biological pathways associated with perturbation of astrocyte (immune pathways) and neuronal (metabolic pathways) EAAT2 expression.ConclusionsOverall, these data support the growing body of evidence for the role of dysregulation of the glutamate system in the pathophysiology of SCZ.

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DLG1

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