Ribozyme-Mediated Suppression of G Protein γ Subunits

Robishaw, Janet D.; Wang, Qin; Schwindinger, William F.

doi:10.1016/s0076-6879(02)44732-5

Cited by 5 publications

(3 citation statements)

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“…Two mutant ribozymes were chemically synthesized in the same way with the following exceptions. The first mutant ribozyme (RZm1) substituted two nucleotides in the catalytic core to destroy cleavage activity (26) and scrambled the flanking arms to prevent any possible antisense effect. The second mutant ribozyme (RZm2) retained catalytic activity but scrambled the flanking arms.…”

Section: Generation Of Hek 293 Cells Stably Expressing Either the D 1mentioning

confidence: 99%

“…2A). For the first mutant ␥ 7 ribozyme (RZm1), the flanking sequences were scrambled to prevent hybridization to the ␥ 7 mRNA, thereby eliminating any possible antisense effect, and the catalytic core region included two substitutions (underlined) that abolish ribozyme cleavage activity (26). For the second mutant ␥ 7 ribozyme (RZm2), only the flanking sequences were scrambled to prevent hybridization to the ␥ 7 mRNA.…”

Section: Generation Of Hek 293 Cells Stably Expressing Either the D 1mentioning

confidence: 99%

“…Consistent with such a role, 12 ␥ subunit genes have been identified that show extensive structural diversity (24). Recently, we used a ribozyme approach to begin to elucidate their functions (23,25,26). This approach identified the ␥ 7 subunit as a specific component of the G protein that couples the ␤-adrenergic receptor, but not the prostaglandin E 1 receptor, to stimulation of adenylylcyclase in HEK 293 cells (23).…”

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Differential Dependence of the D1 and D5Dopamine Receptors on the G Protein γ7 Subunit for Activation of Adenylylcyclase

Wang¹,

Jolly²,

Surmeier³

et al. 2001

Journal of Biological Chemistry

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The D 1 dopamine receptor, G protein ␥ 7 subunit, and adenylylcyclase are selectively expressed in the striatum, suggesting their potential interaction in a common signaling pathway. To evaluate this possibility, a ribozyme strategy was used to suppress the expression of the G protein . Studies suggest that imbalances between these two opposing classes lead to deficiencies in movement and cognitive performance (2, 3). In particular, alterations in the D 1 -like dopamine receptors are implicated in a variety of neurologic and psychiatric disorders, such as Parkinson's disease, Tourette's syndrome, and schizophrenia. Thus, achieving a better understanding of the D 1 -like dopamine receptors and the signaling pathways they activate may suggest more selective therapeutic targets in these diseases.The D 1 and D 5 dopamine receptors stimulate adenylylcyclase activity through their coupling to heterotrimeric G proteins (1, 4 -6). Because the function of these heterotrimeric G proteins was originally ascribed to the ␣ subunit, most research has focused on determining its identity. Of the several ␣ subunits identified to date, reconstitution studies have shown that coupling of D 1 dopamine receptors to adenylylcyclase can be mediated only by the ␣ s and ␣ olf subunits of the G s subclass (4, 5, 7-9). Although sharing 88% amino acid homology, the ␣s and ␣ olf subunits show very divergent expression patterns, ranging from the ubiquitous expression of the ␣ s subunit to the olfactory and neuron-specific expression of the ␣ olf subunit (10). Immunoprecipitation studies (11) have confirmed the interaction between the ␣ s subunit and the D 1 dopamine receptors in cells, whereas in situ hybridization (12, 13) and gene targeting (14) studies have suggested a possible interaction between the ␣ olf subunit and the D 1 dopamine receptor in striatum.By contrast, little effort has focused on determining the identity of the ␤␥ subunits of the G protein despite mounting evidence for their importance in receptor recognition (15,16). Of particular interest, reconstitution studies (17-21) and reverse genetic approaches (22,23) have shown that the nature of the ␥ subunit is an important determinant of its interaction with receptor. Consistent with such a role, 12 ␥ subunit genes have been identified that show extensive structural diversity (24). Recently, we used a ribozyme approach to begin to elucidate their functions (23,25,26). This approach identified the ␥ 7 subunit as a specific component of the G protein that couples the ␤-adrenergic receptor, but not the prostaglandin E 1 receptor, to stimulation of adenylylcyclase in HEK 293 cells (23). Although expressed in a variety of tissues and cell types (27,28), the ␥ 7 subunit expression is most abundant in medium spiny neurons in striatum (13). This pattern of expression is shared by the D 1 dopamine receptor and adenylylcyclase (4, 12, 29 -31), raising the possibility that all of these components may be involved in the same signaling pathway. In the present study, we used the ribozyme ...

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Section: Generation Of Hek 293 Cells Stably Expressing Either the D 1mentioning

confidence: 99%

Section: Generation Of Hek 293 Cells Stably Expressing Either the D 1mentioning

confidence: 99%

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confidence: 99%

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