Studies of the regulated assembly of SNARE complexes in adipocytes

Kioumourtzoglou, Dimitrios; Sadler, Jessica B. A.; Black, Hannah L; Berends, R.; Wellburn, Cassie; Bryant, Nia J.; Gould, Gwyn W.

doi:10.1042/bst20140114

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…It is of interest that both the SM protein Munc18c and its cognate Qa-SNARE Syntaxin4 are phosphorylated on tyrosine residues in response to insulin. In the case of Munc18c this has been shown to regulate SNARE complex assembly at least in vitro (42,43). In response to an insulin stimulus, Munc18c exhibits >10 fold increase in tyrosine phosphorylation in 3T3-L1…”

Section: Tyrosine Phosphorylation Of Sec1/munc18 Proteinsmentioning

confidence: 98%

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

Laidlaw

Livingstone

Al-Tobi

et al. 2017

Biochemical Society Transactions

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Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble -ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion.

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Section: Tyrosine Phosphorylation Of Sec1/munc18 Proteinsmentioning

confidence: 98%

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

Laidlaw

Livingstone

Al-Tobi

et al. 2017

Biochemical Society Transactions

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“…This could be highly relevant for adipocyte function, as caveolae are most prominent in adipocytes, with roles in endocytosis, cholesterol and fatty acid uptake, lipid droplet formation and signal transduction [122,123]. In follow-up studies, we then identified AnxA6-induced cholesterol imbalance to cause mislocalization and dysfunction of several cholesterol-sensitive SNARE proteins in the secretory pathway [72,73], all of which are fundamental for the metabolic response that facilitates GLUT4 translocation in adipocytes [124]. Also, recent findings from our laboratories indicate that cholesterol accumulation in late endosomes of NPC1 mutants promotes the interaction of AnxA6 with the Rab7-GTPase activating protein TBC1D15 (Rentero, Grewal and Enrich, unpublished results), which has recently been implicated in Rab7-dependent pathways that regulate GLUT4 translocation to the cell surface [125].…”

Section: Annexin Expression Patterns In Adipose Tissue and Their Pmentioning

confidence: 99%

“…Along these lines, and as discussed for AnxA6 overexpression and NPC1 deficiency above (see 2.3. ), it is tempting to speculate that late endosomal cholesterol accumulation triggered by AnxA8 downregulation might compromise adipocyte function leading to the improper performance of molecular events in caveolae [63,122,123], or related to insulin signaling and GLUT4 translocation [19,72,73,124].…”

Section: Annexin Expression Patterns In Adipose Tissue and Their Pmentioning

confidence: 99%

Annexins in Adipose Tissue: Novel Players in Obesity

Grewal

Enrich

Rentero

et al. 2019

IJMS

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Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca2+)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.

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“…GLUT4 is the major glucose transporter in muscle and adipose tissue, which constantly cycles between the plasma membrane and intracellular membranes due to the presence of insulin. The GLUT4 endocytic and exocytic itineraries involve a complex interplay of trafficking events and intracellular signalling cascades [ 13 , 14 ]. Calcineurin can dephosphorylate cytoskeletal proteins, such as actin and tubulin [ 15 – 20 ], and proteins involved in endocytosis, such as dynamin and assembly protein 180 kDa (AP)180 [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Calcineurin is an important factor involved in glucose uptake in human adipocytes

et al. 2018

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Calcineurin inhibitors are used in immunosuppressive therapy applied after transplantation, but they are associated with major metabolic side effects including the development of new onset diabetes. Previously, we have shown that the calcineurin inhibiting drugs tacrolimus and cyclosporin A reduce adipocyte and myocyte glucose uptakes by reducing the amount of glucose transporter type 4 (GLUT4) at the cell surface, due to an increased internalization rate. However, this happens without alteration in total protein and phosphorylation levels of key proteins involved in insulin signalling or in the total amount of GLUT4. The present study evaluates possible pathways involved in the altered internalization of GLUT4 and consequent reduction of glucose uptake provoked by calcineurin inhibitors in human subcutaneous adipose tissue. Short- and long-term treatments with tacrolimus, cyclosporin A or another CNI deltamethrin (herbicide) decreased basal and insulin-dependent glucose uptake in adipocytes, without any additive effects observed when added together. However, no tacrolimus effects were observed on glucose uptake when gene transcription and protein translation were inhibited. Investigation of genes potentially involved in GLUT4 trafficking showed only a small effect on ARHGEF11 gene expression (p < 0.05). In conlusion, the specific inhibition of calcineurin, but not that of protein phosphatases, decreases glucose uptake in human subcutaneous adipocytes, suggesting that calcineurin is an important regulator of glucose transport. This inhibitory effect is mediated via gene transcription or protein translation; however, expression of genes potentially involved in GLUT4 trafficking and endocytosis appears not to be involved in these effects.

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Studies of the regulated assembly of SNARE complexes in adipocytes

Cited by 7 publications

References 36 publications

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events

Annexins in Adipose Tissue: Novel Players in Obesity

Calcineurin is an important factor involved in glucose uptake in human adipocytes

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