Regulation of Golgi structure and secretion by receptor-induced G protein βγ complex translocation.
We show that receptor induced G protein betagamma subunit translocation from the plasma membrane to the Golgi allows a receptor to initiate fragmentation and regulate secretion. A lung epithelial cell line, A549, was shown to contain an endogenous translocating G protein gamma subunit and exhibit receptor-induced Golgi fragmentation. Receptor-induced Golgi fragmentation was inhibited by a shRNA specific to the endogenous translocating gamma subunit. A kinase defective protein kinase D and a phospholipase C beta inhibitor blocked receptor-induced Golgi fragmentation, suggesting a role for this process in secretion. Consistent with betagamma translocation dependence, fragmentation induced by receptor activation was inhibited by a dominant negative nontranslocating gamma3. Insulin secretion was shown to be induced by muscarinic receptor activation in a pancreatic beta cell line, NIT-1. Induction of insulin secretion was also inhibited by the dominant negative gamma3 subunit consistent with the Golgi fragmentation induced by betagamma complex translocation playing a role in secretion.
Saini
Deepak Kumar
DK
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Karunarathne
W K Ajith
WK
Angaswamy
Nataraju
N
Saini
Deepti
D
Cho
Joon-Ho
JH
Kalyanaraman
Vani
V
Gautam
Narasimhan
N
D000818:Animals; D045744:Cell Line, Tumor; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D005799:Genes, Dominant; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008870:Microtubules / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction
C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007328:Insulin; D011976:Receptors, Muscarinic; C089212:protein kinase D; D011493:Protein Kinase C; D054799:Phospholipase C beta