Posttranslational Modifications of GLUT4 Affect Its Subcellular Localization and Translocation

Sadler, Jessica B. A.; Bryant, Nia J.; Gould, Gwyn W.; Welburn, Cassie R.

doi:10.3390/ijms14059963

Cited by 36 publications

(24 citation statements)

References 62 publications

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“…Some study described the importance of post-translational modifications of GLUT4 for its subcellular location and translocation [ 39 ]. Among potential post-translational modifications, a conserved N-glycosylation consensus site in GLUT4 is positioned in the first extracellular loop.…”

Section: Discussionmentioning

confidence: 99%

Phylogenesis and Biological Characterization of a New Glucose Transporter in the Chicken (Gallus gallus), GLUT12

Coudert¹,

Pascal²,

Dupont³

et al. 2015

PLoS ONE

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In mammals, insulin-sensitive GLUTs, including GLUT4, are recruited to the plasma membrane of adipose and muscle tissues in response to insulin. The GLUT4 gene is absent from the chicken genome, and no functional insulin-sensitive GLUTs have been characterized in chicken tissues to date. A nucleotide sequence is predicted to encode a chicken GLUT12 ortholog and, interestingly, GLUT12 has been described to act as an insulin-sensitive GLUT in mammals. It encodes a 596 amino acid protein exhibiting 71% identity with human GLUT12. First, we present the results of a phylogenetic study showing the stability of this gene during evolution of vertebrates. Second, tissue distribution of chicken SLC2A12 mRNA was characterized by RT-PCR. It was predominantly expressed in skeletal muscle and heart. Protein distribution was analysed by Western blotting using an anti-human GLUT12 antibody directed against a highly conserved region (87% of identity). An immuno-reactive band of the expected size (75kDa) was detected in the same tissues. Third a physiological characterization was performed: SLC2A12 mRNA levels were significantly lowered in fed chickens subjected to insulin immuno-neutralization. Finally, recruitment of immuno-reactive GLUT12 to the muscle plasma membrane was increased following 1h of intraperitoneal insulin administration (compared to a control fasted state). Thus insulin administration elicited membrane GLUT12 recruitment. In conclusion, these results suggest that the facilitative glucose transporter protein GLUT12 could act in chicken muscle as an insulin-sensitive transporter that is qualitatively similar to GLUT4 in mammals.

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Section: Discussionmentioning

confidence: 99%

Phylogenesis and Biological Characterization of a New Glucose Transporter in the Chicken (Gallus gallus), GLUT12

Coudert¹,

Pascal²,

Dupont³

et al. 2015

PLoS ONE

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“…Mice from two N ‐ethyl‐ N ‐nitrosourea (ENU) lines show abnormal, low amplitude voluntary wheel‐running activity patterns. Circadian activity patterns are double plotted for ease of visualization, with each horizontal line representing 48 hours and successive days plotted along the Y‐axis. Wheel revolutions are depicted as black marks on the horizontal lines.…”

Section: Resultsmentioning

confidence: 99%

“…The premature stop introduced into exon 10 of the gene would likely result in the truncation of the protein and absence of the carboxy terminus. There are several important regulatory elements located in this region of the protein that play a role in its subcellular localization and transmission to the plasma membrane in response to circulating insulin, dietary components and metabolites, or exercise‐related signaling pathways . Thus, although it remains to be determined, it is likely that the phenotypes resulting from the presumably truncated form of Slc2a4 are the result of impairments in its cellular localization.…”

Section: Discussionmentioning

confidence: 99%

“…[54][55][56][57][58] While fasting glucose levels were normal ( Figure 5B and also Figure S1F I-x (F20) T T T T T T T G T T T T G T T T T dietary components and metabolites, or exercise-related signaling pathways. [65][66][67][68][69][70] Thus, although it remains to be determined, it is likely that the phenotypes resulting from the presumably truncated form of Slc2a4 are the result of impairments in its cellular localization.…”

Section: Twiggy Mice Have Metabolic Phenotypes Similar To Glut4 Knomentioning

confidence: 99%

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A novel mutation in Slc2a4 as a mouse model of fatigue

Groot

Castorena

Cox

et al. 2019

Genes Brain and Behavior

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Chronic fatigue is a debilitating disorder with widespread consequences, but effective treatment strategies are lacking. Novel genetic mouse models of fatigue may prove invaluable for studying its underlying physiological mechanisms and for testing treatments and interventions. In a screen of voluntary wheel‐running behavior in N‐ethyl‐N‐nitrosourea mutagenized C57BL/6J mice, we discovered two lines with low body weights and aberrant wheel‐running patterns suggestive of a fatigue phenotype. Affected progeny from these lines had lower daily activity levels and exhibited low amplitude circadian rhythm alterations. Their aberrant behavior was characterized by frequent interruptions and periods of inactivity throughout the dark phase of the light‐dark cycle and increased levels of activity during the rest or light phase. Expression of the behavioral phenotypes in offspring of strategic crosses was consistent with a recessive inheritance pattern. Mapping of phenotypic abnormalities showed linkage with a single locus on chromosome 1, and whole exome sequencing identified a single point mutation in the Slc2a4 gene encoding the GLUT4 insulin‐responsive glucose transporter. The single nucleotide change (A‐T, which we named “twiggy”) was in the distal end of exon 10 and resulted in a premature stop (Y440*). Additional metabolic phenotyping confirmed that these mice recapitulate phenotypes found in GLUT4 knockout mice. However, to the best of our knowledge, this is the first time a mutation in this gene has been shown to result in extensive changes in general behavioral patterns. These findings suggest that GLUT4 may be involved in circadian behavioral abnormalities and could provide insights into fatigue in humans.

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“…GLUT4 is a membrane-spanning protein present on intracellular vesicles in these cell types [3]. In response to insulin, GLUT4 vesicles translocate from the cell interior to the PM where they dock and fuse through interactions between vesicle- and plasma membrane (PM)-localized SNARE proteins [4–9]. Upon vesicle fusion and GLUT4 integration into the PM, GLUT4 facilitates uptake of extracellular glucose - GLUT4 has a high affinity for glucose ( K M ~4 mM), providing a steep gradient for rapid glucose clearance.…”

Section: Munc18c and Maintenance Of Peripheral Insulin Sensitivitymentioning

confidence: 99%

Munc18c: a controversial regulator of peripheral insulin action

Ramalingam

Yoder

et al. 2014

Trends in Endocrinology & Metabolism

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Insulin resistance, a hallmark of impaired glucose tolerance and type 2 diabetes (T2D), arises from dysfunction of insulin action and subsequent glucose uptake by peripheral tissues, predominantly skeletal muscle and fat. Exocytosis of glucose transporter (GLUT4)-containing vesicles facilitated by soluble NSF attachment receptor (SNARE) protein isoforms and Munc18c mediates this glucose uptake. Emerging evidences, including recent human clinical studies, point to pivotal roles for Munc18c in peripheral insulin action in adipose and skeletal muscle. Intriguing new advances are also initiating debates regarding the molecular mechanism(s) controlling Munc18c action. Thus, the objective of this review is to present a balanced perspective of new continuities and controversies surrounding the regulation and requirement for Munc18c in the regulation of peripheral insulin action.

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Posttranslational Modifications of GLUT4 Affect Its Subcellular Localization and Translocation

Cited by 36 publications

References 62 publications

Phylogenesis and Biological Characterization of a New Glucose Transporter in the Chicken (Gallus gallus), GLUT12

Phylogenesis and Biological Characterization of a New Glucose Transporter in the Chicken (Gallus gallus), GLUT12

A novel mutation in Slc2a4 as a mouse model of fatigue

Munc18c: a controversial regulator of peripheral insulin action

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