Type I Calmodulin‐Sensitive Adenylyl Cyclase Is Neural Specific

Xia, Zhengui; Choi, Eui-Ju; Wang, Fan; Blazynski, Christine; Storm, Daniel R.

doi:10.1111/j.1471-4159.1993.tb05852.x

Cited by 173 publications

(84 citation statements)

References 28 publications

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“…The analysis of AC1 and AC8 protein levels through the use of protein immunoblots and immunohistochemistry have yielded consistent and correlated results. The overall patterns of AC1 and AC8 distribution in the brain are in agreement with previously published reports of their mRNA expression (Xia et al, 1991,Matsuoka et al, 1992,Xia et al, 1993,Cali et al, 1994,Matsuoka et al, 1994,Villacres et al, 1995,Tzavara et al, 1996,Schaefer et al, 2000,Nicol et al, 2005 and calcium-stimulated cyclase activity (Villacres et al, 1995,Villacres et al, 1998,Wong et al, 1999. AC1 and AC8 are robustly expressed in the cortex, hippocampus and cerebellum in both early postnatal development and adulthood.…”

Section: Discussionsupporting

confidence: 80%

“…By adulthood, mRNA expression of AC1 is confined to the cerebellum, cortex, dentate gyrus and CA1 regions of the hippocampus, olfactory bulb, pineal gland, and various thalamic nuclei (Xia et al, 1991,Villacres et al, 1995,Tzavara et al, 1996,Matsuoka et al, 1997,Nicol et al, 2005. Notably, AC1 mRNA is expressed only in neurons making it uniquely positioned to regulate neuronal processes, including learning and memory (Xia et al, 1991,Xia et al, 1993.…”

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confidence: 99%

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Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

et al. 2007

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Adenylyl cyclases (ACs) convert ATP to cAMP and therefore, subserve multiple regulatory functions in the nervous system. AC1 and AC8 are the only cyclases stimulated by calcium and calmodulin, making them uniquely poised to regulate neuronal development and neuronal processes such as learning and memory. Here, we detail the production and application of a novel antibody against mouse AC1. Along with AC8 immunohistochemistry, these data reveal distinct and partially overlapping patterns of protein expression in brain during development and adulthood. AC1 protein increased in abundance in the neonatal hippocampus from postnatal day 7 to 14. By adulthood, abundant AC1 protein expression was observed in the mossy fiber tract in the hippocampus and the molecular layer in the cerebellum, with diffuse expression in the cortex and thalamus. AC8 protein levels were abundant during development, with diffuse and increasing expression in the hippocampus that intensified in the CA1/CA2 region by adulthood. AC8 expression was weak in the cerebellum at postnatal day 7 and decreased further by postnatal day 14. Analysis of synaptosome fractions from the adult brain demonstrated robust expression of AC1 in the postsynaptic density and extrasynaptic regions, while expression of AC8 was observed in the presynaptic active zone and extrasynaptic fractions. These findings were confirmed with localization of AC1 and/or AC8 with PSD-95, Tau, synaptophysin and MAP-2 expression throughout the brain. Together, these data provide insight into the functional roles of AC1 and AC8 as reflected by their distinct localization in cellular and subcellular compartments. Keywords cAMP; presynaptic; synaptosome; calcium; calmodulin The ability of the brain to respond and process information dynamically is dependent on intercellular and intracellular neuronal signaling. Adenylyl cyclases (ACs), which generate cAMP, are critical to the integration of this signaling and are essential to processes such as

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Section: Discussionsupporting

confidence: 80%

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confidence: 99%

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

et al. 2007

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“…These data demonstrate that rod adenylyl cyclase belongs to the Ca2+/calmodulin-dependent family of cyclases, which includes types I, III, and VIII (29)(30)(31). Adenylyl cyclase type I is specific to neurons, and its mRNA has been found in high concentration in the cytoplasm of bovine photoreceptor cells (32 This finding has implications for regulation of rod sensitivity by Ca2+, since the light-mediated fall in [Ca2+] could lead to a decrease in the rate of Pd phosphorylation. A potential mechanism for this regulation is depicted in Fig.…”

Section: Methodsmentioning

confidence: 90%

Regulation of phosducin phosphorylation in retinal rods by Ca2+/calmodulin-dependent adenylyl cyclase.

Willardson

Wilkins

Yoshida

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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The phosphoprotein phosducin (Pd) regulates many guanine nucleotide binding protein (G protein)-linked signaling pathways. In visual signal transduction, unphosphorylated Pd blocks the interaction of light-activated rhodopsin with its G protein (Gt) by binding to the fry subunits of Gt and preventing their association with the Gta subunit. When Pd is phosphorylated by cAMP-dependent protein kinase, it no longer inhibits Gt subunit interactions.Thus, factors that determine the phosphorylation state of Pd in rod outer segments are important in controlling the number of Gts available for activation by rhodopsin. The cyclic nucleotide dependencies of the rate of Pd phosphorylation by endogenous cAMP-dependent protein kinase suggest that cAMP, and not cGMP, controls Pd phosphorylation. The synthesis of cAMP by adenylyl cyclase in rod outer segment preparations was found to be dependent on Ca2+ and calmodulin. The Ca2+ dependence was within the physiological range of Ca2+ concentrations in rods (K./2 = 230 + 9 nM) and was highly cooperative (napp = 3.6 + 0.5). Through its effect on adenylyl cyclase and cAMP-dependent protein kinase, physiologically high Ca2+ (1100 nM) was found to increase the rate of Pd phosphorylation 3-fold compared to the rate of phosphorylation at physiologically low Ca2+ (8 nM). No evidence for Pd phosphorylation by other Ca2+-dependent kinases was found. These results suggest that Ca2+ can regulate the light response at the level of Gt activation through its effect on the phosphorylation state of Pd.

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“…As mentioned above, the carboxy terminal part of the C2 domain (C,b) is only present in type I and type VIII adenylyl cyclases, and to a lesser extent in type III. Type I AC has been described as being neural specific [24], and type VIII AC appears to be essentially expressed in the brain [22,25]. There is no homology between type I and type VIII AC in the carboxy terminal part of the molecule.…”

Section: Resultsmentioning

confidence: 99%

Molecular cloning of the human type VIII adenylyl cyclase

et al. 1994

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A cDNA coding for a human type VIII adenylyl cyclase has been isolated from human newborn brain-stem tissue. This cDNA is 6,005 bp long and encodes for a protein of 1251 amino acids, exhibiting the two sets of six transmembrane spanning regions and the hydrophobicity profile typical of other mammalian adenylyl cyclases. Comparison with the rat form shows that they share 97% identity in amino acids. Type VIII adenylyl cyclase is unique in that it has both a long carboxy terminal and a long amino terminal tail. This is the first report on a complete cDNA clone coding for a human adenylyl cyclase. The distribution and regulation of this particular adenylyl cyclase suggest that it may be involved in learning, in memory and in drug dependence.

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Type I Calmodulin‐Sensitive Adenylyl Cyclase Is Neural Specific

Cited by 173 publications

References 28 publications

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Regulation of phosducin phosphorylation in retinal rods by Ca2+/calmodulin-dependent adenylyl cyclase.

Molecular cloning of the human type VIII adenylyl cyclase

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