Immunocytochemical Localization of the G-Protein Sub-unit, Goα, in Rat Heart. Implications for a Role of Goαin Secretion of Cardiac Hormones

Wolf, Wolf-Peter; Spicher, Karsten; Haase, Hannelore; Schulze, Wolfgang

doi:10.1006/jmcc.1998.0679

Cited by 17 publications

(12 citation statements)

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“…Detection of Go protein has also been observed in peripheral neurons and in granules of atrial endocrine cardiomyoctyes [68] . Studies of Go protein knockout mice have revealed that Go signaling controls muscarinic regulation of L-type Ca 2+ channels in the heart [90] .…”

Section: Vagal Regulation In Heartmentioning

confidence: 87%

“…As expected Go is widely expressed in the central nervous system (CNS), including the retina and the olfactory bulb [61][62][63] as well as in the peripheral nervous system, including the superior cervical ganglia and sciatic nerve [64] . In addition, Go expression has been observed in heart tissue [61,[65][66][67][68] and in the endocrine system, including the pituitary gland and pancreatic islets. Go is expressed widely in the brain, however the regional distribution of Go protein is not homogeneous.…”

Section: Go Expression Patternmentioning

confidence: 99%

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Molecular Mechanisms of Go Signaling

2009

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Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane protein in mammalian brains. It functions to couple cell surface receptors to intercellular effectors, which is a critical process for cells to receive, interpret and respond to extracellular signals. Go protein belongs to the pertussis toxin-sensitive Gi/Go subfamily of G proteins. A number of G-protein-coupled receptors transmit stimuli to intercellular effectors through Go. Go regulates several cellular effectors, including ion channels, enzymes, and even small GTPases to modulate cellular function. This review summarizes some of the advances in Go research and proposes areas to be further addressed in exploring the functional role of Go.

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Section: Vagal Regulation In Heartmentioning

confidence: 87%

Section: Go Expression Patternmentioning

confidence: 99%

Molecular Mechanisms of Go Signaling

2009

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“…Expression of the G protein subunit Goa is prominent in the atria and is significantly associated with ANFcontaining secretory granules, as has been shown by immunocytochemistry, and it is virtually absent in ventricular cardiomyocytes (Wolf et al 1998, Bensimon et al 2004. Differential expression profile analysis between rat atria and ventricles using oligonucleotide arrays revealed that the G protein Goa isoform 1 (Goa1) is 2.3-fold more abundantly expressed in the atria than in the ventricles .…”

Section: Introductionmentioning

confidence: 69%

“…In addition, G proteins such as Go, are stretch-sensitive (Van Wagoner 1993), and they are involved in several secretory processes, including ANF secretion, together with K C channels (Ogawa et al 2009). Both light and electron microscopy immunocytochemistry have shown that Goa co-localizes in atrial granules with ANF with a preferential distribution in the granule membrane (Wolf et al 1998, Bensimon et al 2004, Muth et al 2004. The bulk of ventricular cardiomyocytes do not display Goa immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Go protein subunit Goα and the secretory process of the natriuretic peptide hormones ANF and BNP

Roeske

Martinuk

Choudhry

et al. 2015

Journal of Molecular Endocrinology

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Expression of the G protein subunit Goa has been shown to be prominent in the atria of the rat heart and to be significantly associated with atrial natriuretic factor (ANF)-containing atrial-specific secretory granules by immunocytochemistry. In addition, differential expression profile analysis using oligonucleotide arrays has shown that the Goa isoform 1 (Goa1) is 2.3-fold more abundant in the atria than it is in the ventricles. In the present report, we show protein-protein interaction between Goa and ANF by yeast two-hybrid and by immunoprecipitation. A cardiac conditional Goa knockout model developed for the present study showed a 90% decrease in Goa expression and decreased atrial expression and ANF and brain natriuretic peptides (BNP) content. Expression of chromogranin A, a specific atrial granule core constituent, was not affected. Morphometric assessment of atrial tissue showed a very significant decrease in atrial-specific granule density as well as granule core electron density. Atrial electrical activity was not affected. The results obtained are compatible with the suggestion that Goa plays a role in ANF sorting during intracellular vectorial transport and with the presence of a mechanism that preserves the molar relationship between cellular ANF and BNP stores in the face of the decreased production of these hormones.

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“…In the heart, G o is expressed at a much lower level than in the brain. In fact, its existence in the myocardium was long questioned: it was generally believed that G␣ o detected in cardiac tissue originated from G o -rich neuronal cells, until G␣ o expression was unequivocally shown in cardiac myocytes (15,54,55). Deletion of both G␣ o isoforms in the heart was associated with a lack of muscarinic regulation of L-type calcium channels (LCC) in ventricular myocytes (49).…”

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confidence: 99%

Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gα_o* protein

Zhu

Gach²,

Liu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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In contrast to the other heterotrimeric GTP-binding proteins (G proteins) G s and Gi, the functional role of Go is still poorly defined. To investigate the role of G␣o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G␣ o1 ‫ء‬ (G␣ o ‫,)ء‬ the predominant G␣ o isoform in the heart. G␣ o expression was increased 3-to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities. We demonstrate enhanced contractile function in G␣ o‫ء‬ transgenic mice in vivo, along with increased L-type Ca 2ϩ channel current density, calcium transients, and cell shortening in ventricular G␣ o‫-ء‬expressing myocytes compared with wild-type controls. These changes were evident at baseline and maintained after isoproterenol stimulation. Expression levels of all major Ca 2ϩ handling proteins were largely unchanged, except for a modest reduction in Na ϩ /Ca 2ϩ exchanger in transgenic ventricles. In contrast, phosphorylation of the ryanodine receptor and phospholamban at known PKA sites was increased 1.6-and 1.9-fold, respectively, in G␣ o‫ء‬ ventricles. Density and affinity of ␤-adrenoceptors, cAMP levels, and PKA activity were comparable in G␣ o‫ء‬ and wild-type myocytes, but protein phosphatase 1 activity was reduced upon G␣ o‫ء‬ expression, particularly in the vicinity of the ryanodine receptor. We conclude that G␣ o‫ء‬ exerts a positive effect on Ca 2ϩ cycling and contractile function. Alterations in protein phosphatase 1 activity rather than PKA-mediated phosphorylation might be involved in hyperphosphorylation of key Ca 2ϩ handling proteins in hearts with constitutive G␣ o activation. G proteins; signal transduction; calcium; contraction; transgenic mice CARDIAC CONTRACTILE FUNCTION is determined by the intrinsic contractile properties of the heart and is subject to neurohumoral regulation. The main receptors involved in regulating contraction are prototypical G protein-coupled receptors (42). They activate heterotrimeric G proteins that are comprised of ␣-, ␤-, and ␥-subunits (40). G proteins are classified according to their ␣-subunits, because they primarily determine downstream signaling specificity. Several different G proteins are expressed in the heart (53). Members of the G s and G i/o subfamilies play a key role in transmitting extracellular signals that regulate myocyte cell shortening (42): 1) activation of G s protein-coupled receptors (such as ␤-adrenergic receptors) leads to increased adenylyate cyclase activity and cAMP and PKA activation. PKA then phosphorylates several Ca 2ϩ handling and contractile proteins, resulting in increased contraction and relaxation. 2) Activation of cardiac receptors that are coupled to members of the pertussis toxin-sensitive G i/o subfamily (such as A 1 adenosine and M 2 muscarinic receptors) negatively regulate contractile function in mammalian ventricles in the presence of elevated cAMP ("accentuated antagonism"). While G␣ i has the capacity to directly inhib...

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Immunocytochemical Localization of the G-Protein Sub-unit, Goα, in Rat Heart. Implications for a Role of Goαin Secretion of Cardiac Hormones

Cited by 17 publications

References 0 publications

Molecular Mechanisms of Go Signaling

Molecular Mechanisms of Go Signaling

Go protein subunit Goα and the secretory process of the natriuretic peptide hormones ANF and BNP

Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gα_o* protein

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Immunocytochemical Localization of the G-Protein Sub-unit, Goα, in Rat Heart. Implications for a Role of Goαin Secretion of Cardiac Hormones

Cited by 17 publications

References 0 publications

Molecular Mechanisms of Go Signaling

Molecular Mechanisms of Go Signaling

Go protein subunit Goα and the secretory process of the natriuretic peptide hormones ANF and BNP

Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gαo* protein

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Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gα_o* protein