Publications
108 results found
Pernaute B, Sánchez Nieto JM, Pérez-Montero S, et al., 2019, DRP1-mediated regulation of mitochondrial dynamics determines the apoptotic response upon embryonic differentiation, bioRxiv
The changes that drive differentiation create a large potential for the emergence of abnormal cells that need to be removed before they contribute to further development or the germline. This removal is in part achieved by cells becoming hypersensitive to death upon exit of naïve pluripotency. What causes this change in apoptotic response is unknown. Here we identify that it is controlled by the regulator of mitochondrial dynamics DRP1. We show that in mouse, naïve pluripotent cells have fragmented mitochondria due to high DRP1-mediated fission, but upon differentiation, DRP1 activity decreases, inducing mitochondria to fuse and form complex networks. We demonstrate that this decrease in DRP1 activity lowers the apoptotic threshold, as mutation of DRP1 increases the sensitivity to cell death and its over-expression protects against apoptosis. Together, our findings highlight how regulation of mitochondrial dynamics allows cells to adapt their apoptotic response to the changing environment of differentiation.
Buenaventura T, Laughlin WE, Bitsi S, et al., 2018, Agonist binding affinity determines palmitoylation of the glucagon-like peptide-1 receptor and its functional interaction with plasma membrane nanodomains in pancreatic beta cells
<jats:p>The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes and obesity, is known to undergo palmitoylation by covalent ligation of an acyl chain to cysteine 438 in its carboxyl-terminal tail. Work with other GPCRs indicates that palmitoylation can be dynamically regulated to allow receptors to partition into plasma membrane nanodomains that act as signaling hotspots. Here, we demonstrate that the palmitoylated state of the GLP-1R is increased by agonist binding, leading to its segregation and clustering into plasma membrane signaling nanodomains before undergoing internalization in a clathrin-dependent manner. Both GLP-1R signaling and trafficking are modulated by strategies targeting nanodomain segregation and cluster formation, including depletion of cholesterol or expression of a palmitoylation-defective GLP-1R mutant. Differences in receptor binding affinity exhibited by biased GLP-1R agonists, and modulation of binding kinetics with the positive allosteric modulator BETP, influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. Downstream effects on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable.</jats:p>
Moreno-Artero E, Querol E, Rodriguez-Garijo N, et al., 2018, Cocaine-induced pyoderma gangrenosum-like lesions: Levamisole may be not the only culprit. Report of three cases and review of the literature, Annual Meeting of the American-Academy-of-Dermatology (AAD), Publisher: MOSBY-ELSEVIER, Pages: AB78-AB78, ISSN: 0190-9622
Jones B, Buenaventura T, Kanda N, et al., 2018, Targeting GLP-1 receptor trafficking to improve agonist efficacy, Nature Communications, Vol: 9, ISSN: 2041-1723
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a novel series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in β-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments.
Laughlin WE, Buenaventura T, Oqua AI, et al., 2018, Control of glucagon-like peptide-1 receptor (GLP-1R) palmitoylation, lipid raft partitioning, clustering and signalling by biased agonism, Publisher: WILEY, Pages: 54-55, ISSN: 0742-3071
Khan R, Kanda N, Bloom SR, et al., 2018, An investigation into the role of compound 5d in incretin-dependent pancreatic beta cell function, Publisher: WILEY, Pages: 54-54, ISSN: 0742-3071
Garza JG, Aune S, Aznar F, et al., 2018, Micromegas for dark matter searches: CAST/IAXO & TREX-DM experiments, ISSN: 2101-6275
The most compelling candidates for Dark Matter to day are WIMPs and axions. The applicability of gasesous Time Projection Chambers (TPCs) with Micromesh Gas Structures (Micromegas) to the search of these particles is explored within this work. Both particles would produce an extremely low rate at very low energies in particle detectors. Micromegas detectors can provide both low background rates and low energy threshold, due to the high granularity, radiopurity and uniformity of the readout. Small (few cm wide) Micromegas detectors are used to image the ax ion-induced x-ray signal expected in the CERN Axion Solar Telescope (CAST) experiment. We show the background levels obtained in CAST and the prospects to further reduce them to the values required by the Internation Axion Observatory (IAXO). We also present TREX-DM. a scaled-up version of the Micromegas used in axion research, but this time dedicated to the low-mass WIMP detection. TREX-DM is a high-pressure Micromegas-based TPC designed to host a few hundreds of grams of light nuclei (argon or neon) with energy thresholds potentially at the level of 100 eV. The detector is described in detail, as well as the results of the commissioning and characterization phase on surface. Besides, the background model of TREX-DM is presented, along with the anticipated sensitivity of this search, which could go beyond current experimental limits.
Jones B, Bloom S, Buenaventura T, et al., 2018, Control of insulin secretion by GLP-1, Peptides, Vol: 100, Pages: 75-84, ISSN: 0196-9781
Stimulation of insulin secretion by glucagon-like peptide-1 (GLP-1) and other gut-derived peptides is central to the incretin response to ingesting nutriments. Analogues of GLP-1, and inhibitors of its breakdown, have found widespread clinical use for the treatment of type 2 diabetes (T2D) and obesity. The release of these peptides underlies the improvements in glycaemic control and disease remission after bariatric surgery. Given therapeutically, GLP-1 analogues can lead to side effects including nausea, which limit dosage. Greater understanding of the interactions between the GLP-1 receptor (GLP-1R) and both the endogenous and artificial ligands therefore holds promise to provide more efficacious compounds. Here, we discuss recent findings concerning the signalling and trafficking of the GLP-1R in pancreatic beta cells. Leveraging “bias” at the receptor towards cAMP generation versus the recruitment of β-arrestins and extracellular signal-regulated kinases (ERK1/2) activation may allow the development of new analogues with significantly improved clinical efficacy. We describe how, unexpectedly, relatively low-affinity agonists, which prompt less receptor internalisation than the parent compound, provoke greater insulin secretion and consequent improvements in glycaemia.
Podewin T, Ast J, Broichhagen J, et al., 2018, Conditional and reversible activation of class A and B G protein-coupled receptors using tethered pharmacology, ACS Central Science, Vol: 4, Pages: 166-179, ISSN: 2374-7943
Understanding the activation and internalization of G protein-coupled receptors (GPCRs) using conditional approaches is paramount to developing new therapeutic strategies. Here, we describe the design, synthesis, and testing of ExONatide, a benzylguanine-linked peptide agonist of the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR required for maintenance of glucose levels in humans. ExONatide covalently binds to SNAP-tagged GLP-1R-expressing cells, leading to prolonged cAMP generation, Ca2+ rises, and intracellular retention of the receptor. These effects were readily switched OFF following cleavage of the introduced disulfide bridge using the cell-permeable reducing agent beta-mercaptoethanol (BME). A similar approach could be extended to a class A GPCR using GhrelON, a benzylguanine-linked peptide agonist of the growth hormone secretagogue receptor 1a (GHS-R1a), which is involved in food intake and growth. Thus, ExONatide and GhrelON allow SNAP-tag-directed activation of class A and B GPCRs involved in gut hormone signaling in a reversible manner. This tactic, termed reductively cleavable agONist (RECON), may be useful for understanding GLP-1R and GHS-R1a function both in vitro and in vivo, with applicability across GPCRs.
Buenaventura T, Kanda N, Douzenis PC, et al., 2017, A targeted RNAi screen identifies endocytic trafficking factors that control GLP-1 receptor signaling in pancreatic beta cells, Diabetes, Vol: 67, Pages: 385-399, ISSN: 0012-1797
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4. The roles of Huntingtin-interacting protein 1 (HIP1) and the endosomal sorting nexins SNX1 and SNX27 were further characterized in mouse and human beta cell lines and human islets. While HIP1 was required for the coupling of cell surface GLP-1R activation with clathrin-dependent endocytosis, the sorting nexins were found to control the balance between GLP-1R plasma membrane recycling and lysosomal degradation, and, in doing so, determine the overall beta cell incretin responses. We thus identify key modulators of GLP-1R trafficking and signaling that might provide novel targets to enhance insulin secretion in T2D.
Tomas A, Jones S, Vaughan SO, et al., 2017, Stress-specific p38 MAPK activation is sufficient to drive EGFR endocytosis but not its nuclear translocation, Journal of Cell Science, Vol: 130, Pages: 2481-2490, ISSN: 0021-9533
EGF receptor (EGFR) endocytosis is induced by stress in a manner dependent on the p38 MAPK family. Ligand and stresses such as X-rays, reportedly promote nuclear trafficking of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression, and so did not represent nuclear EGFR. UVB and UVC, but not X-ray or UVA, treatment induced p38 activation and EGFR endocytosis, although all of these stresses induced DNA damage, indicating that DNA damage alone is not sufficient to induce EGFR endocytosis. Increased reactive oxygen species (ROS) levels following UVB treatment, compared to that seen with X-rays, do not alone explain differences in p38 activation. UVB, like UVC, induced EGFR accumulation predominantly in perinuclear endosomes, rather than in the nucleus. Our morphological techniques identifying major changes in receptor distribution do not exclude the possibility that small but biologically relevant amounts of EGFR enter the nucleus. This study highlights the importance and limitations of morphological analyses of receptor distribution in understanding signaling outcome.
Jones BJ, Scopelliti R, Tomas A, et al., 2017, Potent prearranged positive allosteric modulators of the glucagon-like peptide-1 receptor, ChemistryOpen, Vol: 6, Pages: 501-505, ISSN: 2191-1363
Drugs that allosterically modulate G protein-coupled receptor (GPCR) activity display higher specificity and may improve disease treatment. However, the rational design of compounds that target the allosteric site is difficult, as conformations required for receptor activation are poorly understood. Guided by photopharmacology, a set of prearranged positive allosteric modulators (PAMs) with restricted degrees of freedom was designed and tested against the glucagon-like peptide-1 receptor (GLP-1R), a GPCR involved in glucose homeostasis. Compounds incorporating a trans-stilbene comprehensively outperformed those with a cis-stilbene, as well as the benchmark BETP, as GLP-1R PAMs. We also identified major effects of ligand conformation on GLP-1R binding kinetics and signal bias. Thus, we describe a photopharmacology-directed approach for rational drug design, and introduce a new class of stilbene-containing PAM for the specific regulation of GPCR activity.
Buenaventura T, Kanda N, Jones B, et al., 2017, Characterisation of glucagon-like peptide-1 (GLP-1) receptor trafficking and its significance for pancreatic beta cell function, DIABETIC MEDICINE, Vol: 34, Pages: 53-53, ISSN: 0742-3071
Podewin T, Broichhagen J, Fine NHF, et al., 2017, Constitutive activation and trafficking of the glucagon-like peptide-1 receptor using tethered pharmacology, Publisher: WILEY, Pages: 41-41, ISSN: 0742-3071
Kanda N, Buenaventura T, Correa Jr IR, et al., 2016, Co-operation between Epidermal Growth Factor Receptor and Glucagon-like Peptide 1 Receptor in Pancreatic Beta Cell Survival during Oxidative stress, EMJ Diabetes, ISSN: 2054-6181
Muriel O, Tomas Catala ADD, Scott CC, et al., 2016, Moesin and cortactin control actin-dependent multivesicular endosome biogenesis., Molecular Biology of the Cell, Vol: 27, Pages: 3305-3316, ISSN: 1059-1524
We have used in vivo and in vitro strategies to study the mechanisms of multivesicular endosomesbiogenesis.We found that, whileannexinA2 andArp2/3 mediate F-actin nucleation and branching, respectively,the ERM proteinmoesinsupports the formation of F-actin networks on early endosomes. We also foundthatmoesin plays no role during endocytosis and recycling to the plasmamembrane, butis absolutely required, much like actin, for early-to-late endosome transport and multivesicular endosome formation. Both actin network formation in vitro and early-to-late endosome transport in vivo also depend on the F-actin binding protein cortactin. Our data thus show that moesin and cortactin are necessary for the formation of F-actin networksthat mediate endosome biogenesis — or maturation— and transport through the degradative pathway. We proposethatthe primary function of endosomal F-actin is to controlthe membrane remodeling process that accompanies endosome biogenesis. We also speculate that this mechanism helps segregate tubular and multivesicular membranes along the recycling and degradation pathways, respectively.
Kanda N, Buenaventura T, Correa IR, et al., 2016, Oxidative stress-induced EGF and GLP-1 receptors cooperate towards pancreatic beta cell survival in response to inflammatory cytokines and glucolipotoxicity, 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S189-S189, ISSN: 0012-186X
Jones B, Buenaventura T, Owen B, et al., 2016, Biased agonism alters GLP-1 receptor trafficking and glucose homeostasis, 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S72-S73, ISSN: 0012-186X
Marzban L, Tomas A, Becker TC, et al., 2016, Erratum. Small Interfering RNA-Mediated Suppression of Proislet Amyloid Polypeptide Expression Inhibits Islet Amyloid Formation and Enhances Survival of Human Islets in Culture. Diabetes 2008;57:3045-3055., Diabetes, Vol: 65, Pages: 818-818, ISSN: 0012-1797
Solomou A, Meur G, Bellomo E, et al., 2015, The Zinc Transporter Slc30a8/ZnT8 Is Required in a Subpopulation of Pancreatic α-Cells for Hypoglycemia-induced Glucagon Secretion., J Biol Chem, Vol: 290, Pages: 21432-21442
SLC30A8 encodes a zinc transporter ZnT8 largely restricted to pancreatic islet β- and α-cells, and responsible for zinc accumulation into secretory granules. Although common SLC30A8 variants, believed to reduce ZnT8 activity, increase type 2 diabetes risk in humans, rare inactivating mutations are protective. To investigate the role of Slc30a8 in the control of glucagon secretion, Slc30a8 was inactivated selectively in α-cells by crossing mice with alleles floxed at exon 1 to animals expressing Cre recombinase under the pre-proglucagon promoter. Further crossing to Rosa26:tdRFP mice, and sorting of RFP(+): glucagon(+) cells from KO mice, revealed recombination in ∼ 30% of α-cells, of which ∼ 50% were ZnT8-negative (14 ± 1.8% of all α-cells). Although glucose and insulin tolerance were normal, female αZnT8KO mice required lower glucose infusion rates during hypoglycemic clamps and displayed enhanced glucagon release (p < 0.001) versus WT mice. Correspondingly, islets isolated from αZnT8KO mice secreted more glucagon at 1 mm glucose, but not 17 mm glucose, than WT controls (n = 5; p = 0.008). Although the expression of other ZnT family members was unchanged, cytoplasmic (n = 4 mice per genotype; p < 0.0001) and granular (n = 3, p < 0.01) free Zn(2+) levels were significantly lower in KO α-cells versus control cells. In response to low glucose, the amplitude and frequency of intracellular Ca(2+) increases were unchanged in α-cells of αZnT8KO KO mice. ZnT8 is thus important in a subset of α-cells for normal responses to hypoglycemia and acts via Ca(2+)-independent mechanisms.
Tomas A, Vaughan SO, Burgoyne T, et al., 2015, WASH and Tsg101/ALIX-dependent diversion of stress-internalized EGFR from the canonical endocytic pathway, Nature Communications, Vol: 6, Pages: 1-13, ISSN: 2041-1723
Stress exposure triggers ligand-independent EGF receptor (EGFR) endocytosis, but its post-endocytic fate and role in regulating signalling are unclear. We show that the p38 MAP kinase-dependent, EGFR tyrosine kinase (TK)-independent EGFR internalization induced by ultraviolet light C (UVC) or the cancer therapeutic cisplatin, is followed by diversion from the canonical endocytic pathway. Instead of lysosomal degradation or plasma membrane recycling, EGFR accumulates in a subset of LBPA-rich perinuclear multivesicular bodies (MVBs) distinct from those carrying EGF-stimulated EGFR. Stress-internalized EGFR co-segregates with exogenously expressed pre-melanosomal markers OA1 and fibrillar PMEL, following early endosomal sorting by the actin polymerization-promoting WASH complex. Stress-internalized EGFR is retained intracellularly by continued p38 activity in a mechanism involving ubiquitin-independent, ESCRT/ALIX-dependent incorporation onto intraluminal vesicles (ILVs) of MVBs. In contrast to the internalization-independent EGF-stimulated activation, UVC/cisplatin-triggered EGFR activation depends on EGFR internalization and intracellular retention. EGFR signalling from this MVB subpopulation delays apoptosis and might contribute to chemoresistance.
Tomas A, Futter CE, 2015, Stress reveals new destination for EGF receptor., Cell Cycle, Vol: 14, Pages: 3343-3344
Ribas EF, Armengaud E, Avignone FT, et al., 2015, The IAXO Helioscope, 7th International Symposium on Large TPCs for Low-Energy Rare Event Detection, Publisher: IOP PUBLISHING LTD, ISSN: 1742-6588
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Iguaz FJ, Aznar F, Castel JF, et al., 2014, Lowering the background level and the energy threshold of Micromegas x-ray detectors for axion searches
Axion helioscopes search for solar axions by their conversion in x-rays in the presence of high magnetic fields. The use of low background x-ray detectors is an essential component contributing to the sensitivity of these searches. In this work, we review the recent advances on Micromegas detectors used in the CERN Axion Solar Telescope (CAST) and proposed for the future International Axion Observatory (IAXO). The actual setup in CAST has achieved background levels below 10-6 keV-1 cm-2 s-1a factor 100 lower than the first generation of Micromegas detectors. This reduction is based on active and passive shielding techniques, the selection of radiopure materials, offline discrimination techniques and the high granularity of the readout. We describe in detail the background model of the detector, based on its operation at CAST site and at the Can-franc Underground Laboratory (LSC), as well as on Geant4 simulations. The best levels currently achieved at LSC are low than 10-7 keV-1 cm-2 s-1 and show good prospects for the application of this technology in IAXO. Finally, we present some ideas and results for reducing the energy threshold of these detectors below 1 keV, using high-transparent windows, autotrigger electronics and studying the cluster shape at different energies. As a high flux of axion-like-particles is expected in this energy range, a sub-keV threshold detector could enlarge the physics case of axion helioscopes.
Vafeiadis T, Arik M, Aune S, et al., 2014, Status of CAST and solar chameleon searches, Pages: 156-162
CERN Axion Solar Telescope (CAST) is the most powerful axion helioscope searching for axions and axion-like particles produced in the Sun. CAST completed its search for solar axions with 3He buffer gas in the magnet bores, covering axion masses up to 1.2 eV. In the absence of excess X-rays it has set the best experimental limit on the axion-photon coupling constant over a broad range of axion masses. In 2013 CAST has improved its sensitivity to solar axions with rest mass below 0.02 eV by using Micromegas detectors and it will continue in 2014 with the implementation of a second X-ray optic and a new type detector (InGrid). In 2013 CAST has extended its sensitivity into the sub-keV energy range using a silicon detector (SDD), to search for solar chameleons, extending its searches to the dark energy sector. This search will be continued in 2014 and 2015 as well with the InGrid detector. Future axion searches can improve the current axion sensitivity by 1 to 1.5 orders of magnitude with a new generation axion telescope (IAXO).
Tomas A, Futter CE, Eden ER, 2013, EGF receptor trafficking: consequences for signaling and cancer, Trends in Cell Biology, Vol: 24, Pages: 26-34, ISSN: 1879-3088
The ligand-stimulated epidermal growth factor receptor (EGFR) has been extensively studied in the analysis of molecular mechanisms regulating endocytic traffic and the role of that traffic in signal transduction. Although such studies have largely focused on mitogenic signaling and dysregulated traffic in tumorigenesis, there is growing interest in the potential role of EGFR traffic in cell survival and the consequent response to cancer therapy. Here we review recent advances in our understanding of molecular mechanisms regulating ligand-stimulated EGFR activation, internalization, and post-endocytic sorting. The role of EGFR overexpression/mutation and new modulators of EGFR traffic in cancer and the response to cancer therapeutics are also discussed. Finally, we speculate on the relationship between EGFR traffic and cell survival.
Vogel JK, Avignone FT, Cantatore G, et al., 2012, IAXO - The International Axion Observatory
The International Axion Observatory (IAXO) is a next generation axion helioscope aiming at a sensitivity to the axion-photon coupling of a few 10−12 GeV−1, i.e. 1-1.5 orders of magnitude beyond sensitivities achieved by the currently most sensitive axion helioscope, the CERN Axion Solar Telescope (CAST). Crucial factors in improving the sensitivity for IAXO are the increase of the magnetic field volume together with the extensive use of x-ray focusing optics and low background detectors, innovations already successfully tested at CAST. Electron-coupled axions invoked to explain the white dwarf cooling, relic axions, and a large variety of more generic axion-like particles (ALPs) along with other novel excitations at the low-energy frontier of elementary particle physics could provide additional physics motivation for IAXO.
Rondas D, Tomas A, Soto-Ribeiro M, et al., 2011, Novel Mechanistic Link between Focal Adhesion Remodeling and Glucose-stimulated Insulin Secretion, Journal of Biological Chemistry, Vol: 287, Pages: 2423-2436, ISSN: 1083-351X
Actin cytoskeleton remodeling is well known to be positively involved in glucose-stimulated pancreatic β cell insulin secretion. We have observed glucose-stimulated focal adhesion remodeling at the β cell surface and have shown this to be crucial for glucose-stimulated insulin secretion. However, the mechanistic link between such remodeling and the insulin secretory machinery remained unknown and was the major aim of this study. MIN6B1 cells, a previously validated model of primary β cell function, were used for all experiments. Total internal reflection fluorescence microscopy revealed the glucose-responsive co-localization of focal adhesion kinase (FAK) and paxillin with integrin β1 at the basal cell surface after short term stimulation. In addition, blockade of the interaction between β1 integrins and the extracellular matrix with an anti-β1 integrin antibody (Ha2/5) inhibited short term glucose-induced phosphorylation of FAK (Tyr-397), paxillin (Tyr-118), and ERK1/2 (Thr-202/Tyr-204). Pharmacological inhibition of FAK activity blocked glucose-induced actin cytoskeleton remodeling and glucose-induced disruption of the F-actin/SNAP-25 association at the plasma membrane as well as the distribution of insulin granules to regions in close proximity to the plasma membrane. Furthermore, FAK inhibition also completely blocked short term glucose-induced activation of the Akt/AS160 signaling pathway. In conclusion, these results indicate 1) that glucose-induced activation of FAK, paxillin, and ERK1/2 is mediated by β1 integrin intracellular signaling, 2) a mechanism whereby FAK mediates glucose-induced actin cytoskeleton remodeling, hence allowing docking and fusion of insulin granules to the plasma membrane, and 3) a possible functional role for the Akt/AS160 signaling pathway in the FAK-mediated regulation of glucose-stimulated insulin secretion.
Rondas D, Tomas A, Halban PA, 2011, Focal Adhesion Remodeling Is Crucial for Glucose-Stimulated Insulin Secretion and Involves Activation of Focal Adhesion Kinase and Paxillin, DIABETES, Vol: 60, Pages: 1146-1157, ISSN: 0012-1797
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Rondas D, Tomas A, Halban P, 2011, Importance of the mechanism of rearrangement of focal adhesions and activation of Focal Adhesion Kinase (FAK) and paxillin upon secretion of insulin, Publisher: MASSON EDITEUR, Pages: A74-A74, ISSN: 1262-3636
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