Artículos de revistas
Ca2+ signals promote GLUT4 exocytosis and reduce its endocytosis in muscle cells
Fecha
2014Registro en:
Am J Physiol Endocrinol Metab 307: E209–E224, 2014.
DOI: 10.1152/ajpendo.00045.2014
Autor
Li, Q.
Zhu, X.
Ishikura, S.
Zhang, D.
Gao, J.
Sun, Y.
Contreras Ferrat, Ariel Eduardo
Foley, K. P.
Lavandero González, Sergio
Yao, Z.
Bilan, P. J.
Klip, A.
Niu, W.
Institución
Resumen
Ca2+ signals promote GLUT4 exocytosis and reduce its endocytosis
in muscle cells. Am J Physiol Endocrinol Metab 307: E209–E224,
2014. First published June 3, 2014; doi:10.1152/ajpendo.00045.2014.—
Elevating cytosolic Ca2 stimulates glucose uptake in skeletal muscle,
but how Ca2+ affects intracellular traffic of GLUT4 is unknown.
In tissue, changes in Ca2+ leading to contraction preclude analysis of
the impact of individual, Ca2 -derived signals. In L6 muscle cells
stably expressing GLUT4myc, the Ca2 ionophore ionomycin raised
cytosolic Ca2 and caused a gain in cell surface GLUT4myc. Extraand
intracellular Ca2 + chelators (EGTA, BAPTA-AM) reversed this
response. Ionomycin activated calcium calmodulin kinase II (CaMKII),
AMPK, and PKCs, but not Akt. Silencing CaMKII or
AMPK 1/ 2 partly reduced the ionomycin-induced gain in surface
GLUT4myc, as did peptidic or small molecule inhibitors of CaMKII
(CN21) and AMPK (Compound C). Compared with the conventional
isoenzyme PKC inhibitor Gö6976, the conventional plus novel PKC
inhibitor Gö6983 lowered the ionomycin-induced gain in cell surface
GLUT4myc. Ionomycin stimulated GLUT4myc exocytosis and inhibited
its endocytosis in live cells. siRNA-mediated knockdown of
CaMKII or AMPK 1/ 2 partly reversed ionomycin-induced
GLUT4myc exocytosis but did not prevent its reduced endocytosis.
Compared with Gö6976, Gö6983 markedly reversed the slowing of
GLUT4myc endocytosis triggered by ionomycin. In summary, rapid
Ca2+ influx into muscle cells accelerates GLUT4myc exocytosis
while slowing GLUT4myc endocytosis. CaMKII and AMPK stimulate
GLUT4myc exocytosis, whereas novel PKCs reduce endocytosis.
These results identify how Ca2+ -activated signals selectively regulate
GLUT4 exocytosis and endocytosis in muscle cells.