Inositol hexakisphosphate promotes dynamin I- mediated endocytosis.
Membrane homeostasis is maintained by exocytosis and endocytosis. The molecular mechanisms regulating the interplay between these two processes are not clear. Inositol hexakisphosphate (InsP(6)) is under metabolic control and serves as a signal in the pancreatic beta cell stimulus-secretion coupling by increasing Ca(2+)-channel activity and insulin exocytosis. We now show that InsP(6) also promotes dynamin I-mediated endocytosis in the pancreatic beta cell. This effect of InsP(6) depends on calcineurin-induced dephosphorylation and is accounted for by both activation of protein kinase C and inhibition of the phosphoinositide phosphatase synaptojanin and thereby formation of phosphatidylinositol 4,5-bisphosphate. In regulating both exocytosis and endocytosis, InsP(6) thus may have an essential integral role in membrane trafficking.
Høy
Marianne
M
Laboratory of Islet Cell Physiology, Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark.
Efanov
Alexander M
AM
Bertorello
Alejandro M
AM
Zaitsev
Sergei V
SV
Olsen
Hervør L
HL
Bokvist
Krister
K
Leibiger
Barbara
B
Leibiger
Ingo B
IB
Zwiller
Jean
J
Berggren
Per-Olof
PO
Gromada
Jesper
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D034284:Dynamin I; D034281:Dynamins; D025802:Electric Capacitance; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000494:pharmacology; D010833:Phytic Acid / Q000378:metabolism* / Q000494:pharmacology
D019269:Phosphatidylinositol 4,5-Diphosphate; D010833:Phytic Acid; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium