Dynamin II regulates hormone secretion in neuroendocrine cells.
The dynamin family of GTP-binding proteins has been implicated as playing an important role in endocytosis. In Drosophila shibire, mutations of the single dynamin gene cause blockade of endocytosis and neurotransmitter release, manifest as temperature-sensitive neuromuscular paralysis. Mammals express three dynamin genes: the neural specific dynamin I, ubiquitous dynamin II, and predominantly testicular dynamin III. Mutations of dynamin I result in a blockade of synaptic vesicle recycling and receptor-mediated endocytosis. Here, we show that dynamin II plays a key role in controlling constitutive and regulated hormone secretion from mouse pituitary corticotrope (AtT20) cells. Dynamin II is preferentially localized to the Golgi apparatus where it interacts with G-protein betagamma subunit and regulates secretory vesicle release. The presence of dynamin II at the Golgi apparatus and its interaction with the betagamma subunit are mediated by the pleckstrin homology domain of the GTPase. Overexpression of the pleckstrin homology domain, or a dynamin II mutant lacking the C-terminal SH3-binding domain, induces translocation of endogenous dynamin II from the Golgi apparatus to the plasma membrane and transformation of dynamin II from activity in the secretory pathway to receptor-mediated endocytosis. Thus, dynamin II regulates secretory vesicle formation from the Golgi apparatus and hormone release from mammalian neuroendocrine cells.
Yang
Z
Z
Baker Medical Research Institute, Department of Pathology and Immunology, Monash University Medical School, Commercial Road, Prahran, Victoria 3181, Australia.
Li
H
H
Chai
Z
Z
Fullerton
M J
MJ
Cao
Y
Y
Toh
B H
BH
Funder
J W
JW
Liu
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins; D034284:Dynamin I; D034286:Dynamin III; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000502:physiology; D001615:beta-Endorphin / Q000378:metabolism; D018909:src Homology Domains
D017931:DNA Primers; D029721:Drosophila Proteins; D006728:Hormones; D011990:Receptors, Transferrin; D001615:beta-Endorphin; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034286:Dynamin III; D034281:Dynamins; C439628:shi protein, Drosophila