Complement 1q-like-3 protein inhibits insulin secretion from pancreatic β-cells via the cell adhesion G protein–coupled receptor BAI3

Gupta, Rajesh; Nguyen, Dan C.; Schaid, Michael D.; Lei, Xia; Balamurugan, Appakalai N.; Wong, G. William; Kim, Jeong a.; Koltes, James E.; Kimple, Michelle E.; Bhatnagar, Sushant

doi:10.1074/jbc.ra118.005403

Cited by 36 publications

(31 citation statements)

References 62 publications

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“…In addition, C1ql3 was shown to be involved in synapse formation/maintenance underlying formation of fear memories (Martinelli et al, 2016). Peripherally, C1ql3 inhibits insulin secretion in pancreatic b cells (Gupta et al, 2018), whereas C1ql4 acts as a repressor of myoblast fusion (Hamoud et al, 2014) and was recently identified as a novel regulator of testosterone secretion in the testis (Tan et al, 2019). ADGRB3 utilizes selective domains to engage with different C1ql proteins.…”

Section: A Complement C1q-like 1-4mentioning

confidence: 99%

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

2019

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Section: A Complement C1q-like 1-4mentioning

confidence: 99%

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

2019

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“…Forty-eight hours after siRNA knockdown or scramble control, Min6 or Ins1 cells were stimulated in low (2.8 mM) or stimulatory (16.7 mM) glucose in Krebs-Ringer bicarbonate/ HEPES buffer (KRBH) for 30 min at 37°C, similar to that described in Ref. 72. Supernatant media, with secreted insulin, were collected.…”

Section: Gsismentioning

confidence: 99%

LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet β-cell function

Wade

Liu

Bethea

et al. 2019

Journal of Biological Chemistry

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Edited by Joel M. Gottesfeld Diabetes is characterized by a loss of ␤-cell mass, and a greater understanding of the transcriptional mechanisms governing ␤-cell function is required for future therapies. Previously, we reported that a complex of the Islet-1 (Isl1) transcription factor and the co-regulator single-stranded DNA-binding protein 3 (SSBP3) regulates the genes necessary for ␤-cell function, but few proteins are known to interact with this complex in ␤-cells. To identify additional components, here we performed SSBP3 reverse-cross-linked immunoprecipitation (ReCLIP)-and MSbased experiments with mouse ␤-cell extracts and compared the results with those from our previous Isl1 ReCLIP study. Our analysis identified the E3 ubiquitin ligases ring finger protein 20 (RNF20) and RNF40, factors that in nonpancreatic cells regulate transcription through imparting monoubiquitin marks on histone H2B (H2Bub1), a precursor to histone H3 lysine 4 trimethylation (H3K4me3). We hypothesized that RNF20 and RNF40 regulate similar genes as those regulated by Isl1 and SSBP3 and are important for ␤-cell function. We observed that Rnf20 and Rnf40 depletion reduces ␤-cell H2Bub1 marks and uncovered several target genes, including glucose transporter 2 (Glut2), MAF BZIP transcription factor A (MafA), and uncoupling protein 2 (Ucp2). Strikingly, we also observed that Isl1 and SSBP3 depletion reduces H2Bub1 and H3K4me3 marks, suggesting that they have epigenetic roles. We noted that the RNF complex is required for glucose-stimulated insulin secretion and normal mitochondrial reactive oxygen species levels. These findings indicate that RNF20 and RNF40 regulate ␤-cell gene expression and insulin secretion and establish a link between Isl1 complexes and global cellular epigenetics.

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“…C1QL1‐BAI3 signaling regulates both the strengthening of a winner and the elimination of loser climbing fibers on a Purkinje cell, leading to correct 1‐to‐1 climbing fiber‐Purkinje cell innervation (2). BAI3 mediates the inhibitory effects of C1QL3 on insulin secretion from pancreatic β‐cells (6). A recent report showed that C1QL4 signals via BAI3 to negatively control myoblast fusion (7).…”

mentioning

confidence: 99%

Expression patterns of C1ql4 and its cell‐adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis

Tan

Chen

et al. 2019

FASEB j.

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C1q‐like 4 (C1QL4), a novel member of the C1q‐ and TNF‐related protein family, was found to be highly expressed in rodent and human testis. However, the localization, developmental, and hormonally regulated expression and biologic function of C1ql4 in the testis have not been investigated. Here, we demonstrated that C1ql4 mRNA and protein levels in murine testes gradually increased from the postnatal period to the adult stage and were up‐regulated by LH in vivo. In situ hybridization demonstrated that the distribution and expression levels of C1ql4 mRNA varied at different developmental stages, although C1ql4 mRNA was detected in the seminiferous tubule and interstitial Leydig cells. Recombinant C1QL4 did not affect cell proliferation but did increase testosterone production in TM3 Leydig cells, as well as in cultured seminiferous tubules. C1QL4‐induced testosterone secretion in Leydig cells was accompanied by increased expression of steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes. During this process, the c‐Raf/extracellular signal‐regulated protein kinase kinases 1 and 2/ERK1/2/mitogen‐ and stress‐activated protein kinase‐1 and cAMP/PKA/cAMP‐responsive element binding protein signaling cascades were activated by C1QL4. The cell‐adhesion GPCR brain‐specific angiogenesis inhibitor 3 (BAI3), a putative receptor of C1QL4, was detected in the seminiferous tubule and interstitial Leydig cells during testicular development. Knockdown of Bai3 expression in Leydig cells led to a reduction in Star expression, accompanied by increases in phosphorylation of ERK1/2 and intercellular cAMP levels. However, C1QL4‐induced StAR expression was not completely suppressed in the Bai3‐deficient Leydig cells, and phosphorylation of ERK1/2 and intercellular cAMP levels were not significantly changed before and after C1QL4 stimulation. Our results suggested that although BAI3 played a role in C1QL4‐induced steroidogenesis, there was an unidentified receptor that mediated C1QL4‐activated testosterone secretion in Leydig cells through phosphorylation of ERK1/2 and up‐regulation of intracellular cAMP levels. Taken together, our results showed, for the first time to our knowledge, that C1QL4 served as a novel acute regulator of testosterone secretion, and BAI3 functioned as a new receptor that is involved in steroidogenesis in Leydig cells. BAI3‐independent ERK1/2 activation and cAMP activation mediated C1QL4‐induced testosterone secretion. This study expanded the reproductive roles and mechanisms of C1QL4 and BAI3 signaling pathways.—Tan, A., Ke, S., Chen, Y., Chen, L., Lu, X., Ding, F., Yang, L., Tang, Y., Yu, Y. Expression patterns of C1ql4 and its cell‐adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis. FASEB J. 33, 4893–4906 (2019). http://www.fasebj.org

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Complement 1q-like-3 protein inhibits insulin secretion from pancreatic β-cells via the cell adhesion G protein–coupled receptor BAI3

Cited by 36 publications

References 62 publications

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

Beyond the Ligand: Extracellular and Transcellular G Protein–Coupled Receptor Complexes in Physiology and Pharmacology

LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet β-cell function

Expression patterns of C1ql4 and its cell‐adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis

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