Endocytosis, Recycling, and Regulated Exocytosis of Glucose Transporter 4

Foley, Kevin P.; Boguslavsky, Shlomit; Klip, Amira

doi:10.1021/bi2000356

Cited by 141 publications

(151 citation statements)

References 177 publications

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“…Microcystin-LR was from Enzo Life Sciences (Farmingdale, NY). 2-Deoxy-D- [1,[2][3] The AS160 KO-first ES cells (Tbc1d4tm1a(EUCOMM)Hmgu, clone no. HEPD0601_5_F08) were purchased from the European Mouse Mutant Cell Repository (Neuherberg, Germany), and used for blastocyst injection to obtain the AS160 f/f mice ( Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

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The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia

Xie

Chen

et al. 2016

Diabetes

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The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that the deletion of AS160 decreased GLUT4 levels in a cell/ tissue-autonomous manner. Consequently, skeletal muscle-specific deletion of AS160 caused postprandial hyperglycemia and hyperinsulinemia. The pathogenic effects of AS160 deletion are mainly, if not exclusively, due to the loss of its RabGAP function since the RabGAP-inactive AS160 R917K mutant mice phenocopied the AS160 knockout mice. The inactivation of RabGAP of AS160 promotes lysosomal degradation of GLUT4, and the inhibition of lysosome function could restore GLUT4 protein levels. Collectively, these findings demonstrate that the RabGAP activity of AS160 maintains GLUT4 protein levels in a cell/tissue-autonomous manner and its inactivation causes lysosomal degradation of GLUT4 and postprandial hyperglycemia and hyperinsulinemia.

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Section: Methodsmentioning

confidence: 99%

“…After the removal of insulin, GLUT4 on the cell surface is internalized back into the cell through endocytosis and sorted into GSVs or recycling endosomes (3). Some of the recycled GLUT4 can also undergo degradation through lysosomes (4).…”

mentioning

confidence: 99%

The Inactivation of RabGAP Function of AS160 Promotes Lysosomal Degradation of GLUT4 and Causes Postprandial Hyperglycemia and Hyperinsulinemia

Xie

Chen

et al. 2016

Diabetes

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“…The formation of this fusion pore allows neurotransmitter molecules to exit the pore as it expands. The general theory of exocytosis suggests that it is an all or none process and that the synaptic vesicle membrane and proteins are then rapidly retrieved and reutilized for the formation of new synaptic vesicles, a process called endocytosis (Foley et al 2011;Wu et al 2014). These vesicles are reloaded with transmitter for another round of exocytosis, a cycle that is repeated many times and can be studied in nerve terminals that have no connection with the neuronal cell body.…”

Section: An Overview Of Exocytosis and Endocytosismentioning

confidence: 99%

The evidence for open and closed exocytosis as the primary release mechanism

Ren

Mellander

Keighron

et al. 2016

Quart. Rev. Biophys.

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Abstract. Exocytosis is the fundamental process by which cells communicate with each other. The events that lead up to the fusion of a vesicle loaded with chemical messenger with the cell membrane were the subject of a Nobel Prize in 2013. However, the processes occurring after the initial formation of a fusion pore are very much still in debate. The release of chemical messenger has traditionally been thought to occur through full distention of the vesicle membrane, hence assuming exocytosis to be all or none. In contrast to the all or none hypothesis, here we discuss the evidence that during exocytosis the vesicle-membrane pore opens to release only a portion of the transmitter content during exocytosis and then close again. This open and closed exocytosis is distinct from kiss-and-run exocytosis, in that it appears to be the main content released during regular exocytosis. The evidence for this partial release via open and closed exocytosis is presented considering primarily the quantitative evidence obtained with amperometry.1. An overview of exocytosis and endocytosis 2 2. Techniques to monitor exocytosis 5 2.1. Patch clamp 6 2.2. Amperometry 6 2.3. Patch amperometry 7 2.4. Cyclic voltammetry 7 2.5. Fluorescence microscopy imaging 83. Traditional models of exocytosis 94. Evidence where partial release during exocytosis appears to be dominant 11 4.1. The total content of a secretory vesicle is greater than the amount released 11 4.2. The majority of exocytotic events are followed by immediate endocytosis 12 4.3. Full distention of the vesicle may not be necessary for quantal release 13 4.4. A flickering fusion pore might regulate quantal release and vesicle recycling 15 4.5. Nanometer-sized pores can be seen as 'feet' associated with amperometric spikes 17 3. Release appears to be only a fraction of vesicle content in mammalian brains 23 7.4. Impact cytometry of adrenal cell vesicles shows a significantly larger catecholamine content then that released 23 7.5. Impact cytometry has been used to measure vesicle content in live cells and this quantity is greater than the amount released 23 7.6. Full distention of the vesicle is not necessary for the measured amperometric current during exocytotic release 23 7.7. Fast changes in cell environment alter the amount of messenger released 23 7.8. Patch amperometry measurements reveal a greater amount of release 23 7.9. Postspike 'feet' are observed with an amperometric spike 23Acknowledgements 24

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“…This may be explained by a normalization of GLUT4 protein concentration at the skeletal muscle by leptin in the fasted state as seen in our fasting skeletal muscle GLUT4 content, which is comparable to the control group. Since, GLUT4 is usually stored within the cell in specialized compartments called GLUT4 storage vesicles (GSV) and translocated to the cell membrane when needed [17], we assume that chronic administration of leptin was able to maintain normal levels of skeletal muscle GLUT4 content and thus was able to maintain normal fasting glucose level in spite of hyperinsulinaemia.…”

Section: Resultsmentioning

confidence: 99%