Molecular mechanism of photoreceptor g protein signaling

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Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
Project Description:
The long-term objective of the proposed program is to investigate molecular mechanisms underlying signaling via the photoreceptor G protein transducin (Gt) in the vertebrate photoreceptor cells. The role and general regulation of transducin during the activation and turnoff phases in visual excitation are well understood. However, our understanding of certain aspects of the function and mechanisms of Gt remains incomplete. Recent studies have confirmed and extended earlier findings of light-dependent translocation of Gt from the outer segments to the inner segments and other compartments of photoreceptor cells. Very little is known about the mechanism of Gtalpha translocation or new potential Gtalpha interacting proteins in the inner segments. Our search for photoreceptor-specific proteins containing G-protein regulatory (GPR)-motifs has revealed that a member of GPR-family, LGN, is present in the inner segments and the synaptic layer of photoreceptor cells, where, as suggested by the preliminary data, it interacts with Gtalpha. The interaction between LGN and Gtalpha, its functional significance, and novel LGN-binding proteins in the retina will be investigated using biochemical approaches in vitro, a mouse model with disrupted LGN/Gtalpha binding, and an LGN knockout mouse model. Another direction of this proposal stems from our previous studies that have indicated the possibility of a novel mechanism of congenital stationary night blindness. Our results suggested a loss of visual signaling in the Nougaret form of night blindness due to the effector defect of the Gtalpha mutant G38D. The molecular mechanism of Nougaret night blindness and the dominant nature of the G38D mutation will be elucidated using a transgenic GtalphaG38D mouse model. The mice will be examined by a combination of immunohistochemical, biochemical, and electrophysiological approaches. Initial characterization of the transgenic mice indicated that the G38D mutant displays deficient light-dependent translocation. This supports the hypothesis that the movement of Gtalpha towards the inner segment is triggered by a specific conformation and/or interactions of transducin. The Gtalpha determinants for the initiation of translocation will be investigated in the RGS9 knockout mice, GTPase-deficient GtalphaQ200L and PDE6-interaction deficient GtalphaI208A transgenic mice. Overall, these studies will help to achieve a better understanding of Gt signaling mechanisms as well as other G protein signaling systems and will provide information relevant to retinal diseases.
 
Project Terms:
visual phototransduction transducin protein structure function G protein biological signal transduction visual photoreceptor protein protein interaction phosphorylation phosphodiesterases rhodopsin posttranslational modifications binding proteins chimeric proteins protein binding site directed mutagenesis genetically modified animals laboratory mouse crosslink
Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
Project Categories:
• Natural Sciences > Aging Diseases and Pathology > Neurodegenerative diseases
 
Other Information:
Fiscal Year: 2000
Project Start Date: 1 May 2000
Project End Date: 30 June 2009
Administering Institute Or Center: EY
 
Project Funding Information:
Total Funding: $368,750
Year Funding Organization Total Funding, $
2004 NATIONAL EYE INSTITUTE $368,750
Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
Project number Project title Organization FY Funding Organization FY Total Cost
2R01EY012682-05Molecular Mechanism of Photoreceptor G Protein SignalingUNIVERSITY OF IOWA2004NATIONAL EYE INSTITUTE
$368,750
5R01EY010843-11Regulation of Retinal cGMP PhosphodiesterasesUNIVERSITY OF IOWA2004NATIONAL EYE INSTITUTE
$331,875
5R01EY012682-04MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALINGUNIVERSITY OF IOWA2003NATIONAL EYE INSTITUTE
$220,500
2R01EY010843-10Regulation of Retinal cGMP PhosphodiesterasesUNIVERSITY OF IOWA2003NATIONAL EYE INSTITUTE
$331,313
5R01EY012682-03MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALINGUNIVERSITY OF IOWA2002NATIONAL EYE INSTITUTE
$220,500
5R01EY010843-09REGULATION OF RETINAL CYCLIC GMP PHOSPHODIESTERASESUNIVERSITY OF IOWA2002NATIONAL EYE INSTITUTE
$223,231
5R01EY012682-02MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALINGUNIVERSITY OF IOWA2001NATIONAL EYE INSTITUTE
$220,500
5R01EY010843-08REGULATION OF RETINAL CYCLIC GMP PHOSPHODIESTERASESUNIVERSITY OF IOWA2001NATIONAL EYE INSTITUTE
$216,729
1R01EY012682-01A1MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALINGUNIVERSITY OF IOWA2000NATIONAL EYE INSTITUTE
$217,351
5R01EY010843-07REGULATION OF RETINAL CYCLIC GMP PHOSPHODIESTERASESUNIVERSITY OF IOWA2000NATIONAL EYE INSTITUTE
$210,416
5R01EY010843-12Regulation of Retinal cGMP PhosphodiesterasesUNIVERSITY OF IOWA2005NATIONAL EYE INSTITUTE
$331,875
5R01EY012682-06Molecular Mechanism of Photoreceptor G Protein SignalingUNIVERSITY OF IOWA2005NATIONAL EYE INSTITUTE
$368,750
5R01EY010843-13Regulation of Retinal cGMP PhosphodiesterasesUNIVERSITY OF IOWA2006NATIONAL EYE INSTITUTE
$324,077
5R01EY012682-07Molecular Mechanism of Photoreceptor G Protein SignalingUNIVERSITY OF IOWA2006NATIONAL EYE INSTITUTE
$360,084
5R01EY010843-14Regulation of Retinal cGMP PhosphodiesterasesUNIVERSITY OF IOWA2007NATIONAL EYE INSTITUTE
$322,262
5R01EY012682-08Molecular Mechanism of Photoreceptor G Protein SignalingUNIVERSITY OF IOWA2007NATIONAL EYE INSTITUTE
$358,068
2R01EY010843-15A1Regulation of Retinal cGMP phosphodiesterasesUNIVERSITY OF IOWA2008NATIONAL EYE INSTITUTE
$371,090
5R01EY012682-09Molecular Mechanism of Photoreceptor G Protein SignalingUNIVERSITY OF IOWA2008NATIONAL EYE INSTITUTE
$350,907
5R01EY010843-16Regulation of Retinal cGMP phosphodiesterasesUNIVERSITY OF IOWA2009NATIONAL EYE INSTITUTE
$370,972
3R01EY010843-16S1Regulation of Retinal cGMP phosphodiesterasesUNIVERSITY OF IOWA2009NATIONAL EYE INSTITUTE
$54,082
Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
Project number Project title Principal investigator
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Project Title: Molecular mechanism of photoreceptor g protein signaling
Principal Investigators (PI): ARTEMYEV NIKOLAI O
Project Number: 2R01EY012682-05
Organization: UNIVERSITY OF IOWA
 
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