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The Metabotropic Channel: Discoveries on How the Alpha 7 Nicotinic Receptor Signals Through G Proteins
Başlık:
The Metabotropic Channel: Discoveries on How the Alpha 7 Nicotinic Receptor Signals Through G Proteins
Yazar:
King, Justin, author.
ISBN:
9780438109933
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (228 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Nadine Kabbani Committee members: Kim Blackwell; M. Saleet Jafri; Jim Olds.
Özet:
Classically two distinct types of neurotransmitter receptors are known to exist, "ionotropic" ion conducting channels, which operate as rapid ion exchange conduits between the cell and its environment, and "metabotropic" receptors, which activate longer lived intracellular molecular cascades. This thesis challenges these assumptions by examining interactions between the alpha7 nicotinic acetylcholine receptor channel (nAChR) and heterotrimeric GTP binding (G) protein signaling in neural and immune cells. Here, I define a novel G protein binding cluster (GPBC) within the intracellular region of the alpha7 nAChR protein and create a dominant negative mutant that is deficient in G protein binding. Studies demonstrate that alpha7 nAChRs operate through both ionotropic and metabotropic activity to drive calcium induced calcium release, and G protein induced calcium release from local endoplasmic reticulum, respectively. Metabotropic G protein signaling appears to extend the time course of alpha7 nAChR function thereby enhancing intracellular calcium release and calcium associated cytoskeletal signaling at the growth cone. These findings provide evidence on a new mechanism of channel activity, which can be of value for understanding receptor function and treating disease.
Notlar:
School code: 0883
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(691938.1) | 691938-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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