Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles

Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
The Journal of Cell Biology (Impact Factor: 9.69). 04/2005; 168(6):921-8. DOI: 10.1083/jcb.200408182
Source: PubMed

ABSTRACT We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.

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    ABSTRACT: Because of their great abundance, high specific surface area, layer charge, laminar morphology, and chemical reactivity towards both neutral and charged species, clay minerals are of great importance to agriculture, industry, and the environment. The presence of iron in the structures of clay minerals infuses an additional facet into their importance. This is because the oxidation state of iron can be rather easily modified in situ and such a change can evoke profound differences in the surface-chemical and structural behaviour of the mineral. Examples of clay mineral properties that are greatly affected by changes in iron oxidation state are swelling in water, CEC, cation fixation capacity, surface area, clay mineral-organic interactions, surface pH, reduction potential, ability to transform chlorinated organic compounds, and ability to degrade pesticides and thereby alter their toxicity to mammals. Reduction of structural iron from Fe3+ to Fe2+ in smectites has been observed both in the laboratory and in situ in the field. Bacteria are second only to dithionite in their effectiveness to reduce structural iron in clay mineral and are the most important agent responsible for this phenomenon in natural soils and sediments. Because the manipulation of the iron oxidation state causes such large changes in chemical and physical behaviour and because such changes can be invoked under field conditions, a great opportunity exists to exploit this phenomenon for a myriad of purposes beneficial to mankind. Although such exploitation has yet to occur to any large extent, it has found application in the remediation of subsurface soils contaminated with radioactive and other harmful metals. Studies are also beginning to emerge that recognise this as an important factor in sustaining the fertility and use of flooded soils. Clearly, other opportunities will arise for its use in creating designer minerals for industrial uses. Challenges and many unanswered questions still face those who study redox processes of iron in clay minerals, especially with respect to the mechanisms governing the electron transfer and the linkages between Fe2+ and surface behaviour. How is the electron passed from the outer surfaces of the clay mineral layers into the octahedral sheet? What are the precise energies associated with this process? The exact surface forces altered by the redox process appear to be both coulombic and non-coulombic, but the precise nature of the latter is not well understood. What is the mechanism for electron transfer from bacteria to clay mineral layers-is it done through a direct membrane contact or are electron shuttles or mediators utilised? Is the mechanism the same for all bacteria? Even though the phenomenon of iron redox in clay minerals has been studied for several decades, the number of scientists participating in such studies is still rather small. Interest in this field of inquiry is beginning to grow, however, and answers to these and other questions are anticipated to be forthcoming. On a personal note, this author has been the beneficiary of many intriguing twists and turns along the path in the realm of iron redox chemistry, which has provided a most interesting, challenging, and rewarding perspective to his study of clay science. He has been awed by the intricacies of Nature as seen at such a seemingly insignificant level in the grand overall scheme of things, but which reveal such majestic order and complexity at the same time. His feelings about this are well captured in the words of the poet Elizabeth Barrett Browning (1937), who declared, "Earth's crammed with heaven, and every common bush afire with God; only he who sees takes off his shoes." My shoes are off!
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