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Dissecting the Molecular Basis of Neurotransmitter Signaling Modulation by GINIP /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Dissecting the Molecular Basis of Neurotransmitter Signaling Modulation by GINIP /Alex Luebbers.
作者:	Luebbers, Alex,
面頁冊數:	1 electronic resource (180 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-07, Section: B.
附註:	Advisors: Garcia-Marcos, Mikel; Zaia, Joseph Committee members: Layne, Matthew D.; Harris, David A.; Davison, Ian.
Contained By:	Dissertations Abstracts International85-07B.
標題:	Biology.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30817448
ISBN:	9798381432213

Dissecting the Molecular Basis of Neurotransmitter Signaling Modulation by GINIP /
Luebbers, Alex,

Dissecting the Molecular Basis of Neurotransmitter Signaling Modulation by GINIP /Alex Luebbers. - 1 electronic resource (180 pages)

Source: Dissertations Abstracts International, Volume: 85-07, Section: B.

G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins (Gαβγ), which together form one of the most important signaling axes found in the cell. Because GPCRs are very common targets for therapeutic drugs, the mechanisms underlying their regulation are of high biomedical importance. Downstream of GPCR activation, there are many cytoplasmic proteins that regulate the activity of G proteins, providing an opportunity for therapeutic intervention. The neuronal protein GINIP binds directly to Gαi and is believed to play a role in modulating GPCR-mediated neurotransmission, an exquisitely-balanced process whereby dysregulation leads to neurological disorders including chronic pain and epilepsy. However, the molecular and structural determinants of GINIP underlying and required for proper regulation of G protein signaling downstream of GPCRs are unclear. In the studies presented here, we dissect the molecular and structural basis by which GINIP regulates G proteins after receptor activation and contributes to the fine-tuning of neurotransmitter responses in the nervous system. First, we revealed a new paradigm of G protein regulation by GINIP whereby it biases GPCR responses favoring Gβγ-mediated signaling to the detriment of Gα-mediated signaling. Second, we demonstrated that GINIP uses specific residues in the first loop of the PHD domain to physically engage Gαi by adopting a binding mode similar to that of G protein effectors like adenylyl cyclase, which is in turn required for the subsequent modulation of G protein signaling. Together, these insights advance our understanding of how GPCR signaling is fine-tuned by GINIP to set the tone of neurotransmission. Characterizing this layer of G protein regulation after receptor activation is crucial for developing novel therapeutic approaches to target diseases that arise from dysregulated GPCR signaling.

English

ISBN: 9798381432213Subjects--Topical Terms:

188667
Biology.
Subjects--Index Terms:

G protein

Dissecting the Molecular Basis of Neurotransmitter Signaling Modulation by GINIP /
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