ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface expression

Giguère, Hugo; Dumont, Audrey-Ann; Berthiaume, Jonathan; Oliveira, Vanessa de Carvalho; Laberge, Gino; Auger‐Messier, Mannix

doi:10.1038/s41598-018-31784-w

Cited by 14 publications

(8 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell size was measured through surface area calculation [(axb)/2] under fluorescence microscopy following anti-α-actinin staining. Data demonstrated that LPS increased α-actinin (a cardiomyocyte specific marker and a hypertrophic marker gene) (31,32) expression levels. However, the effect produced by LPS was reversed by LTL (Myocyte area: From 7.9 to 5.7 µm 2 , P<0.05; From 7.9 to 4.0 µm 2 , P<0.01; Figs.…”

Section: Resultsmentioning

confidence: 99%

Luteolin suppresses lipopolysaccharide‑induced cardiomyocyte hypertrophy and autophagy in�vitro

Liu

Wang

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

Luteolin (LTL) serves essential roles in a wide variety of biological processes. Lipopolysaccharide (LPS) can lead to myocardial hypertrophy and autophagy. However, the roles of LTL on LPS-induced cardiomyocyte hypertrophy and autophagy in rat cardiomyocytes have not yet been fully elucidated. In the present study, the morphology of cultured rat cardiomyocytes was observed under an inverted microscope. Cell viability was detected by MTT assay. α-Actinin and microtubule-associated protein 1 light chain 3 (LC3) expression levels were measured by immunofluorescence assay. In addition, the expression levels of atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP), LC3, and autophagy- and Wnt signaling pathway-associated genes were analyzed by reverse transcription-quantitative polymerase chain reaction or western blot assays. The results indicated that LTL increased the cell viability of cardiomyocytes treated with LPS. LTL decreased the expression of cardiac hypertrophy associated markers (ANP and BNP). LTL decreased α-actinin and LC3 expression levels in LPS-treated cardiomyocytes. It was also demonstrated that LTL suppressed the mRNA and protein expression levels of LPS-mediated autophagy and Wnt signaling pathway-associated genes. In addition, it was demonstrated that silencing of β-catenin inhibited LPS-induced cardiomyocyte hypertrophy and the formation of autophagosomes. Thus, the present study suggested that LTL protected against LPS-induced cardiomyocyte hypertrophy and autophagy in rat cardiomyocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

Luteolin suppresses lipopolysaccharide‑induced cardiomyocyte hypertrophy and autophagy in�vitro

Liu

Wang

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…While RASA3 has demonstrated affinity for PtdIns(4,5)P 2 and PtdIns(3,4,5)P 3 [34,41,92] to our knowledge we provide the first evidence of its affinity for PtdIns(3,4)P 2 , and this interaction may support PtdIns(3,4)P 2 in promoting sustained α IIb β 3 outside-in signalling. Indeed, given the association between integrin activation and PtdIns(3,4)P 2 generation in platelets, it is noteworthy that PtdIns(3,4)P 2 effectors such as RASA3, PHLDB1 [75,76] and ADAP1 [84] identified in our screen are linked to integrin signalling and function.…”

Section: Discussionmentioning

confidence: 75%

“…MTMR5 is an inactive phosphatase that has been proposed to act as a scaffolding protein and a GEF for RABfamily small GTPases [77][78][79], while ADAP1 is a GAP with dual PH domains; the first holds affinity for PtdIns(3,4,5)P 3 , and the second for both PtdIns(3,4,5)P 3 and PtdIns(3,4)P 2 [43]. ADAP1 has been shown to possess GAP activity for ARF6, a small GTPase with roles in vesicular trafficking (including platelet endocytosis [80]) and cytoskeletal arrangements, and accordingly ADAP1 has been implicated in control of the actin cytoskeleton, and the trafficking and surface expression of GPCRs and integrins [43,[81][82][83][84]. While GAB1 and 2 hold various functional roles in different cell types and are known to possess affinity for 3-phosphoinositides [85,86], GAB3 has received more limited functional characterisation.…”

Section: Discussionmentioning

confidence: 99%

Identification of PtdIns(3,4)P2 effectors in human platelets using quantitative proteomics

Durrant

Moore

Bayliss

et al. 2020

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

After decades in PtdIns(3,4,5)P 3 's shadow, PtdIns(3,4)P 2 has now emerged as a bona fide regulator of important cellular events, including endocytosis and cell migration. New understanding of PtdIns(3,4)P 2 's cellular roles has been possible via novel approaches to observe and quantify cellular PtdIns(3,4)P 2 dynamics, alongside methods to target the kinases and phosphatases governing phosphoinositide turnover. Despite this, the mechanisms by which PtdIns(3,4)P 2 orchestrates its cellular roles remain more poorly understood, most notably because, to date, few PtdIns(3,4)P 2 effectors have been identified. Here, we develop and apply an affinity-proteomics strategy to conduct a global screen for PtdIns(3,4)P 2 interactors in human platelets; a primary cell type with striking PtdIns(3,4)P 2 accumulation. Through an integrated approach, coupling affinity capture of PtdIns(3,4)P 2 -binding proteins to both label-free and isobaric tag-based quantitative proteomics, we identify a diverse PtdIns(3,4)P 2 interactome. Included are long-established PtdIns(3,4)P 2 -binding proteins such as PLEKHA1, PLEKHA2, AKT and DAPP1, and a host of potentially novel effectors, including MTMR5, PNKD, RASA3 and GAB3. The PtdIns(3,4)P 2 interactome shows an enrichment of pleckstrin homology (PH) domain-containing proteins, and through bioinformatics and array analyses we characterise the PH domain of MTMR5 and define its phosphoinositide selectivity. The interactome is also diverse in function, including several proteins known to support protein trafficking and cytoskeletal mobilisation. Such proteins have the ability to drive key platelet events, and to fulfil recently-defined roles for PtdIns(3,4)P 2 in a wider range of cell types. Moreover, this study will serve as a valuable resource for the future characterisation of effector-driven PtdIns(3,4)P 2 function.

show abstract

“…More complex physiological functions of ADAP1 have recently been discovered. It has been shown that ADAP1 inhibits hypertrophy in cardiomyocytes (Giguere et al 2018). In Rat Neonatal Ventricular Cardiomyocytes (RNVC), ADAP1 overexpression blocks Mek1ca-induced hypertrophy and reduces cell surface β1-integrin expression effecting the hypertrophic process of cardiomyocytes (Giguere et al 2018).…”

Section: Acapsmentioning

confidence: 99%

“…It has been shown that ADAP1 inhibits hypertrophy in cardiomyocytes (Giguere et al 2018). In Rat Neonatal Ventricular Cardiomyocytes (RNVC), ADAP1 overexpression blocks Mek1ca-induced hypertrophy and reduces cell surface β1-integrin expression effecting the hypertrophic process of cardiomyocytes (Giguere et al 2018). A review by (Stricker and Reiser 2014) have highlighted the central role of ADAP 1 in neuronal differentiation and neurodegenerative diseases.…”

Section: Acapsmentioning

confidence: 99%

Functional characterisation of EFA6R, a possible biomarker for Epithelial Ovarian Cancer

Tamaddon-Jahromi¹

View full text Add to dashboard Cite

Background: EFA6R functions as a guanine nucleotide exchange factor for Arf6 -a Ras-like GTPase protein that potently regulates tumour progression. EFA6R is consistently expressed in healthy ovarian epithelium, but is drastically downregulated in the vast majority of Epithelial Ovarian Cancers (EOC). Therefore, EFA6R could be a novel biomarker for EOC.Aim: 1. Study EFA6R expression in Epithelial Ovarian Cancer (EOC) cell lines and tissues. 2. Identify the mechanisms of EFA6R downregulation and its role in mediating cellular phenotype. 3. Delineate the expression, localisation and cellular functions of EFA6R isoforms. Results: In EOC Tissue cDNA array, 73% of 192 samples exhibited little or significantly less EFA6R expression than healthy samples. In tissue microarrays containing 80 individual cases of different grades, EFA6R expression was lost with tumour progression. Similar downregulation was observed in tissue lysates (6/7 samples) and 10/10 OC cell lines. In SKOV-3 cells treated with demethylation agent 5-aza-2'deoxycytidine (5-Aza-Cdr) EFA6R expression was restored at mRNA and protein level; ~10-fold increase in EFA6R expression corresponded with significant attenuation of cell migration (~60% decrease in migration observed in Ibidi wound healing assay and ~ 5-fold decrease in migration and invasion in transwell assay). Exogenous expression of EFA6R plasmid DNA constructs showed that EFA6R localisation to the plasma membrane requires the PH and to a lesser extent, the CC domain. There, it functions as an Arf6-specific GEF, modulating actin stress fibres. Endogenous expression of EFA6R was observed in HEK293 and ReN cells. In the former, it potentially regulates bintegrin expression and in the latter, it plays a part in neuronal differentiation.Conclusion: EFA6R loss of function can be attributed to epigenetic mechanisms. Its downregulation, increases migration and metastasis through Arf6-independent pathways. One of the EFA6R isoforms has limited expression in some cell lines where it may play an important physiological role Contents

show abstract

ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface expression

Cited by 14 publications

References 60 publications

Luteolin suppresses lipopolysaccharide‑induced cardiomyocyte hypertrophy and autophagy in�vitro

Luteolin suppresses lipopolysaccharide‑induced cardiomyocyte hypertrophy and autophagy in�vitro

Identification of PtdIns(3,4)P2 effectors in human platelets using quantitative proteomics

Functional characterisation of EFA6R, a possible biomarker for Epithelial Ovarian Cancer

Contact Info

Product

Resources

About