SNAP-tag-enabled super-resolution imaging reveals constitutive and agonist-dependent trafficking of GPR56 in pancreatic β-cells

Olaniru, Oladapo E.; Cheng, Jordan; Ast, Julia; Arvaniti, Anastasia; Atanes, Patricio; Huang, Guo Cai; King, Aileen; Jones, Peter M.; Broichhagen, Johannes; Hodson, David J.; Persaud, Shanta J.

doi:10.1016/j.molmet.2021.101285

Cited by 9 publications

(11 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also shown that the knock-down of GPR56 (GPR56-KD) leads to β-cell dysfunction, reduced cell viability, and attenuates the beneficial effect of Collagen Type III (Coll III) on β-cell function [ 18 ]. Our observations thus corroborate reported findings showing that, although GPR56-KO mice have normal islet vascularization and only mildly impaired glucose tolerance, the activation of GPR56 by Coll III increases islet insulin secretion and enhances cell viability [ 19 , 25 ]. GPR56 has, thus, been mainly linked to protecting β-cells from apoptosis, but it is similarly important for the insulin secretory function of β-cells.…”

Section: Introductionsupporting

confidence: 92%

“…The rationale for the present investigations is the documented role of GPR56 in pancreatic β-cell survival and secretory function [ 18 , 19 , 21 , 25 , 33 ]. The expression level of GPR56 is positively correlated with the transcript level of a great number of genes with a beneficial impact on the β-cell fate in human pancreatic islets [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…This observation confirms previous studies that GPR56 plays a role in inflammation and has been identified as an inhibitory receptor, suppressing the pro-inflammatory activity of cytotoxic lymphocytes [ 38 ]. Likewise, cytokine-induced β-cell apoptosis is prevented by Coll III, but not by a simple overexpression of GPR56 [ 25 ]. However, the delineation of the inflammatory mechanism in GPR56-deficient β-cells extends beyond the scope of the present work and merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…TXNIP is known to activate the NLRP3 inflammasome, generating interleukin-1β, thereby contributing to impaired β-cell function [ 37 , 42 ]. An increased cAMP formation exerts β-cell protection in part by promoting TXNIP proteosomal degradation [ 42 ], an effect that could explain coll III protection from cytokine-induced apoptosis in human islets [ 25 ]. The overexpression of VDAC1 and its mistargeting to the β-cell plasma membrane leads to a loss of ATP, the crucial metabolic coupling factor in GSIS [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane

et al. 2023

View full text Add to dashboard Cite

The activation of G Protein-Coupled Receptor 56 (GPR56), also referred to as Adhesion G-Protein-Coupled Ceceptor G1 (ADGRG1), by Collagen Type III (Coll III) prompts cell growth, proliferation, and survival, among other attributes. We investigated the signaling cascades mediating this functional effect in relation to the mitochondrial outer membrane voltage-dependent anion Channel-1 (VDAC1) expression in pancreatic β-cells. GPR56KD attenuated the Coll III-induced suppression of P70S6K, JNK, AKT, NFκB, STAT3, and STAT5 phosphorylation/activity in INS-1 cells cultured at 20 mM glucose (glucotoxicity) for 72 h. GPR56-KD also increased Chrebp, Txnip, and Vdac1 while decreasing Vdac2 mRNA expression. In GPR56-KD islet β-cells, Vdac1 was co-localized with SNAP-25, demonstrating its plasma membrane translocation. This resulted in ATP loss, reduced cAMP production and impaired glucose-stimulated insulin secretion (GSIS) in INS-1 and human EndoC βH1 cells. The latter defects were reversed by an acute inhibition of VDAC1 with an antibody or the VDAC1 inhibitor VBIT-4. We demonstrate that Coll III potentiates GSIS by increasing cAMP and preserving β-cell functionality under glucotoxic conditions in a GPR56-dependent manner by attenuating the inflammatory response. These results emphasize GPR56 and VDAC1 as drug targets in conditions with impaired β-cell function.

show abstract

Section: Introductionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The SNAP technology was introduced in 2003 by Keppler et al 50 SNAP covalently links O 6 benzylguanine (BG) derivatives to O 6 -alkylguanine-DNAalkyltransferase (AGT) proteins using a cysteine residue at the active site, and has been engineered to abolish any DNAbinding activity. [50][51][52] The SNAP tag was later modified to react with O 2 -benzyl-cytosine derivatives (CLIP tag) for in vivo and in vitro applications. 51 SNAP and CLIP tags have mainly been used to fluorescently label fused proteins for studying PPIs, although they have been also used creatively for other purposes.…”

Section: Bifunctional Modalities Employing Engineered Proteins For Pr...mentioning

confidence: 99%

Proximity-inducing modalities: the past, present, and future

et al. 2023

View full text Add to dashboard Cite

show abstract

Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells

McLaughlin,

Weaver,

Syed

et al. 2023

Comprehensive Physiology

View full text Add to dashboard Cite

Type 2 diabetes (T2D) affects more than 32.3 million individuals in the United States, creating an economic burden of nearly $966 billion in 2021. T2D results from a combination of insulin resistance and inadequate insulin secretion from the pancreatic β cell. However, genetic and physiologic data indicate that defects in β cell function are the chief determinant of whether an individual with insulin resistance will progress to a diagnosis of T2D. The subcellular organelles of the insulin secretory pathway, including the endoplasmic reticulum, Golgi apparatus, and secretory granules, play a critical role in maintaining the heavy biosynthetic burden of insulin production, processing, and secretion. In addition, the mitochondria enable the process of insulin release by integrating the metabolism of nutrients into energy output. Advanced imaging techniques are needed to determine how changes in the structure and composition of these organelles contribute to the loss of insulin secretory capacity in the β cell during T2D. Several microscopy techniques, including electron microscopy, fluorescence microscopy, and soft X‐ray tomography, have been utilized to investigate the structure‐function relationship within the β cell. In this overview article, we will detail the methodology, strengths, and weaknesses of each approach. © 2024 American Physiological Society. Compr Physiol 14:5243‐5267, 2024.

show abstract

SNAP-tag-enabled super-resolution imaging reveals constitutive and agonist-dependent trafficking of GPR56 in pancreatic β-cells

Cited by 9 publications

References 66 publications

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane

Proximity-inducing modalities: the past, present, and future

Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells

Contact Info

Product

Resources

About