Positive Regulation of Insulin Signaling by Neuraminidase 1

Dridi, Larbi; Seyrantepe, Volkan; Fougerat, Anne; Pan, Xuefang; Bonneil, Éric; Thibault, Pierre; Moreau, Allain; Mitchell, Grant A.; Heveker, Nikolaus; Cairo, Christopher W.; Issad, Tarik; Hinek, Alexander; Pshezhetsky, Alexey V.

doi:10.2337/db12-1825

Cited by 79 publications

(89 citation statements)

References 49 publications

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“…This effect could be explained by the activation of subunit Neu-1, which is a sialic acid hydrolase that specifically clips off terminally located sialic acid on protein surfaces. Our findings support the recent work of Dridi et al (45), who demonstrated that Neu-1 can interact and desialylate IR. Surprisingly, they showed that the interaction is insulin-dependent and upregulates IR signaling.…”

Section: Discussionsupporting

confidence: 93%

Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

et al. 2013

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Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the β-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES.

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Section: Discussionsupporting

confidence: 93%

Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

et al. 2013

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“…In this respect, a compelling observation was that ASMCs exposed to therapeutic concentrations of insulin have de novo formation of elastic fibers, independently of their rate of proliferation. These results were confirmed in fibroblasts from patients with sialidosis, which appear to proliferate faster, respond more strongly to recombinant growth factors than normal fibroblasts, and have impaired insulin-induced phosphorylation of downstream signaling proteins [68, 59]. The latter observation suggests an interesting link between NEU1/EBP-dependent elastogenesis and vascular pathologies associated with diabetes, many of which are linked to elastic fiber disease [69].…”

Section: The Lmc and Its Components In Tissue And Cell Homeostasismentioning

confidence: 84%

“…Indeed, treatment of ASMCs with an exogenous sialidase was shown to abolish the mitogenic responses to growth factors, such as PDGF-BB and IGF-2, through removal of the sialic acids from their respective cognate receptors PDGF-R and IGF-1R [59]. Similarly, in rat skeletal L6 myoblasts alterations of the sialic acid content of the insulin receptor (IR) by mouse-derived Neu1 or C. perfringens sialidase were shown to modulate the proliferative capacity of these cells in response to insulin signaling [67, 68]. In this respect, a compelling observation was that ASMCs exposed to therapeutic concentrations of insulin have de novo formation of elastic fibers, independently of their rate of proliferation.…”

Section: The Lmc and Its Components In Tissue And Cell Homeostasismentioning

confidence: 99%

Lysosomal multienzyme complex: pros and cons of working together

Bonten

Annunziata

d’Azzo

2013

Cell. Mol. Life Sci.

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The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates requires the synergistic action of multiple hydrolases that usually work in a stepwise fashion. This catalytic machinery explains the existence of lysosomal enzyme complexes that can be dynamically assembled and disassembled to efficiently and quickly adapt to the pool of substrates to be processed or degraded, adding extra tiers to the regulation of the individual protein components. An example of such a complex is the one composed of three hydrolases that are ubiquitously but differentially expressed: the serine carboxypeptidase, Protective Protein/Cathepsin A (PPCA), the sialidase, Neuraminidase-1 (NEU1), and the glycosidase β-Galactosidase (β-GAL). Next to this ‘core’ complex, the existence of sub-complexes, that may contain additional components, and function at the cell surface or extracellularly, suggests as yet unexplored functions of these enzymes. Here we review how studies of basic biological processes in the mouse models of three lysosomal storage disorders, galactosialidosis, sialidosis, and GM1-gangliosidosis, revealed new and unexpected roles for the three respective affected enzymes, Ppca, Neu1 and β-Gal, that go beyond their canonical degradative activities. These findings have broadened our perspective on their functions and may pave the way for the development of new therapies for these lysosomal storage disorders.

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“…At the plasma membrane, NEU1 has been shown to be required for signal transduction and elastogenesis through the elastin receptor complex91011 and to be involved in the modulation of insulin receptor signaling1213, regulation of integrin beta 414, TLR415, Trk A16, PDGF-BB and IGF receptors17, EGF and MUC1 receptors18 and more recently CD3119. Consequently, NEU1 now emerges not only as a catabolic enzyme but also as a key actor involved in cell signaling regulation20.…”

mentioning

confidence: 99%

New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability

Maurice

Baud

Bocharova

et al. 2016

Sci Rep

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Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139–159 (TM1) and 316–333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.

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Positive Regulation of Insulin Signaling by Neuraminidase 1

Cited by 79 publications

References 49 publications

Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

Lysosomal multienzyme complex: pros and cons of working together

New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability

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