Activity-dependent potentiation of large dense-core vesicle release modulated by mitogen-activated protein kinase/extracellularly regulated kinase signaling.
Large dense-core vesicles (LDCVs), containing neuropeptides, hormones, and amines, play a crucial role in the activation of the sympathetic nervous system and synaptic modulation. In some secretory cells, LDCVs show activity-dependent potentiation (ADP), which represents enhancement of subsequent exocytosis, compared with the previous one. Here we report the signaling mechanism involved in ADP of LDCV release. First, ADP of LDCV release, induced by repetitive stimulation of nicotinic acetylcholine receptors (nAChRs), was augmented by increasing calcium influx, showing calcium dependence of ADP. Second, translocation of vesicles was involved in ADP. Electron microscope analysis revealed that nAChR stimulation resulted in LDCV translocation to the plasma membrane and increase of fused LDCVs in response to repetitive stimulation was observed by amperometry. Third, we provide evidence for involvement of MAPK signaling in ADP. MAPK signaling was activated by nAChR-induced calcium influx, and ADP as well as vesicle translocation was suppressed by inhibition of MAPK signaling with MAPK kinase blockers, such as PD 098059 and U0126. Fourth, PD 098059 inhibited nAChR stimulation-induced F-actin disassembly, which has been reported to control vesicle translocation. Taken together, we suggest that ADP of LDCV release is modulated by calcium-dependent activation of MAPK signaling via regulating F-actin disassembly.
Park
Yong-Soo
YS
Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang 790-784, Republic of Korea.
Jun
Dong-Jae
DJ
Hur
Eun-Mi
EM
Lee
Sun-Kyong
SK
Suh
Byung-Sun
BS
Kim
Kyong-Tai
KT
D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism; D004594:Electrophysiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015151:Immunoblotting; D020935:MAP Kinase Signaling System; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D021381:Protein Transport; D011978:Receptors, Nicotinic / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D015398:Signal Transduction
D000199:Actins; D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D011978:Receptors, Nicotinic; C113580:U 0126; D000244:Adenosine Diphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium