GPR56: An adhesion GPCR involved in brain development, neurological disorders and cancer

Ganesh, Raksha A.; Venkataraman, Krishnan; Sirdeshmukh, Ravi

doi:10.1016/j.brainres.2020.147055

Cited by 16 publications

(11 citation statements)

References 109 publications

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“…The expression of CD97/ADGRE5, a member of the aGPCR family, was significantly upregulated in breast, thyroid, stomach, pancreas, esophageal cancer and CRC and was associated with the metastasis of a variety of tumors [17][18][19]. The expression of GPR56/ADGRL1, another member of the aGPCR family, was upregulated in CRC tissues [20,21]. Abdul Aziz et al [22] analyzed the gene expression profiles of tumor tissues from 78 CRC patients by microarray and followed the survival time of these patients.…”

Section: Discussionmentioning

confidence: 99%

ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Sun¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

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Metastasis is a key factor that affects the prognosis of colorectal cancer (CRC), and patients with metastasis have limited treatment options and poor prognoses. EGF, latrophilin, and seven transmembrane domains containing 1 (ELTD1/ADGRL4) are members of the adhesion G protein-coupled receptor (aGPCR) superfamily. In this study, high expression of ELTD1 was correlated with lymph node metastasis and poor outcomes in CRC patients. Both in vitro and in vivo studies showed that ELTD1 markedly promoted the invasion and metastasis of CRC. Moreover, ELTD1 accelerated the transcriptional activity of MMP2, which could rescue the impaired invasiveness of CRC cells caused by the downregulation of ELTD1 expression. In conclusion, our study suggests that ELTD1 might be a potential novel target for the treatment of CRC metastasis.

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Section: Discussionmentioning

confidence: 99%

ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Sun¹,

Zhang²,

Chen³

et al. 2021

Int. J. Biol. Sci.

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“… Neurological disorders –The role of CAMs in neurological disorders is well documented. The connections with depression, schizophrenia, Parkinson’s disease, autism spectrum disorders, Alzheimer’s disease, Down syndrome, epilepsy, and others were found [ 12 , 22 , 25 , 33 , 34 , 35 ]. When NCAMs are attached to the polysialic acid (PolySia-NCAMs), they play a leading role in schizophrenia as vital regulators of synaptic plasticity, cell migration, axon guidance, and synapse formation [ 35 ].…”

Section: Cams In a Health And A Diseasementioning

confidence: 99%

“…Depressed patients’ brains have morphological changes in cortical and subcortical regions, HC shrinkage, and decreased amygdala volume [ 50 ]. Furthermore, morphological changes in neurons, synaptic spines, and dendrites were found in discussed conditions [ 51 , 52 ], and the changes in CAMs were observed [ 12 , 22 , 25 , 33 , 34 , 35 ]. Adhesive changes follow morphological changes, and eventually, neurotransmission may be dysregulated [ 12 , 53 ].…”

Section: The Idea Of Assessing the Physicochemical Phenomenon Of Adhe...mentioning

confidence: 99%

Physicochemical Principles of Adhesion Mechanisms in the Brain

Stachowicz

2023

IJMS

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The brain functions through neuronal circuits and networks that are synaptically connected. This type of connection can exist due to physical forces that interact to stabilize local contacts in the brain. Adhesion is a fundamental physical phenomenon that allows different layers, phases, and tissues to connect. Similarly, synaptic connections are stabilized by specialized adhesion proteins. This review discusses the basic physical and chemical properties of adhesion. Cell adhesion molecules (CAMs) such as cadherins, integrins, selectins, and immunoglobulin family of cell adhesion molecules (IgSF) will be discussed, and their role in physiological and pathological brain function. Finally, the role of CAMs at the synapse will be described. In addition, methods for studying adhesion in the brain will be presented.

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“…Orphan G protein-coupled receptors (oGPCRs) are pathologically related to many human diseases such as schizophrenia, type 2 diabetes, hyperactivity, cognitive impairment, brain malformation, Alzheimer's disease and others [1][2][3][4][5][6][7] . Many oGPCRs including the adhesion family (aGPCRs) are constitutively active receptors, presenting additional technical hurdles for deorphanization 8 .…”

Section: Introductionmentioning

confidence: 99%

The activation mechanism and antibody binding mode for orphan GPR20

Lin

Jiang

et al. 2023

Cell Discov

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GPR20 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for gastrointestinal stromal tumors (GIST) owing to its differentially high expression. An antibody-drug conjugate (ADC) containing a GPR20-binding antibody (Ab046) was recently developed in clinical trials for GIST treatment. GPR20 constitutively activates Gi proteins in the absence of any known ligand, but it remains obscure how this high basal activity is achieved. Here we report three cryo-EM structures of human GPR20 complexes including Gi-coupled GPR20 in the absence or presence of the Fab fragment of Ab046 and Gi-free GPR20. Remarkably, the structures demonstrate a uniquely folded N-terminal helix capping onto the transmembrane domain and our mutagenesis study suggests a key role of this cap region in stimulating the basal activity of GPR20. We also uncover the molecular interactions between GPR20 and Ab046, which may enable the design of tool antibodies with enhanced affinity or new functionality for GPR20. Furthermore, we report the orthosteric pocket occupied by an unassigned density which might be essential for exploring opportunities for deorphanization.

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GPR56: An adhesion GPCR involved in brain development, neurological disorders and cancer

Cited by 16 publications

References 109 publications

ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Physicochemical Principles of Adhesion Mechanisms in the Brain

The activation mechanism and antibody binding mode for orphan GPR20

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