期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 43, 页码 9913-9918出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2376-05.2005
关键词
adenylate cyclase; knock-out mice; hippocampus; phosphatase; calcium; signal transduction
资金
- NIMH NIH HHS [P50 MH058880, P50-MH58880] Funding Source: Medline
- NINDS NIH HHS [NS20498, R01 NS020498, NS37056, R01 NS037056] Funding Source: Medline
Ca2+ -stimulated adenylyl cyclases are important for several forms of neuroplasticity because they couple activity-dependent Ca2+ increases to cAMP in neurons. For example, the calmodulin-stimulated adenylyl cyclases, AC1 and AC8, are required for hippocampus-dependent memory and long-lasting long-term potentiation. To identify other mechanisms for Ca2+ stimulation of adenylyl cyclases, cultured hippocampal neurons from transgenic mice lacking both AC1 and AC8 [ double knock-out (DKO) mice] were analyzed for Ca2+ stimulation of intracellular cAMP. Surprisingly, neurons from DKO mice showed significant Ca2+ -stimulated cAMP accumulation that was blocked by inhibitors of calcineurin [PP2B (protein phosphatase 2B)], a Ca2+ -activated protein phosphatase. Analysis of cultured neurons from calcineurin -/- mice confirmed that hippocampal neurons exhibit a calcineurin-dependent cAMP increase, which may contribute to some forms of neuroplasticity.
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