High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS160 inhibition in adipocytes.
Glucose entry into cells is mediated by a family of facilitative transporter proteins (GLUTs). In mammals, GLUT4 is expressed in insulin-sensitive tissues and is responsible for the postprandial uptake of glucose. In fish, GLUT4 also mediates insulin-regulated glucose entry into cells but differs from mammalian GLUT4 in its affinity for glucose and in protein motifs known to be important for the traffic of GLUT4. In this study, we have characterized the intracellular and plasma membrane (PM) traffic of two orthologs of GLUT4 in fish, trout (btGLUT4) and salmon (okGLUT4), that do not share the amino terminal FQQI targeting motif of mammalian GLUT4. btGLUT4 (FQHL) and, to a lesser extent, okGLUT4 (FQQL) showed higher basal PM levels, faster traffic to the PM after biosynthesis, and earlier acquisition of insulin responsiveness than rat GLUT4. Furthermore, btGLUT4 showed a similar profile of internalization than rat GLUT4. Expression of the dominant-interfering AS160-4P mutant caused a significant decrease in the insulin-induced PM levels of okGLUT4 and rat GLUT4 and, to a lesser extent, of btGLUT4, suggesting that btGLUT4 has reduced retention into the IRC. Contrary to rat GLUT4 and okGLUT4, the presence of btGLUT4 at the PM under insulin-stimulated conditions was not affected by coexpression of a dominant-interfering GGA mutant. These data suggest that fish GLUT4 follow a different trafficking pathway to the PM compared with rat GLUT4 that seems to be relatively independent of GGA. These results indicate that the regulated trafficking characteristics of GLUT4 have been modified during evolution from fish to mammals.
Capilla
Encarnación
E
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
Díaz
Mònica
M
Hou
June Chunqiu
JC
Planas
Josep V
JV
Pessin
Jeffrey E
JE
D016475:3T3 Cells; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004734:Energy Metabolism; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D051379:Mice; D017684:Oncorhynchus kisutch / Q000378:metabolism*; D020033:Protein Isoforms; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D014337:Trout / Q000378:metabolism*
D001786:Blood Glucose; D029941:Fish Proteins; D051275:Glucose Transporter Type 4; D020033:Protein Isoforms