Ανάλυση νέων σηματοδοτικών μονοπατιών των οπιοειδών υποδοχέων που οδηγούν σε αλλαγές της συναπτοσωμικής πλαστικότητας

Doctoral Dissertation uoadl:1308638 559 Read counter

Unit:
Τομέας Φυσιολογίας Ζώων και Ανθρώπου
Library of the School of Science
Deposit date:
2012-06-13
Year:
2012
Author:
Γεωργαντά Ειρήνη-Μαρία
Dissertation committee:
Σπύρος Ευθυμιόπουλος (Αναπλ. Καθηγητής-Επιβλέπων), Ζαφειρούλα Γεωργούση (Διευθύντρια Ερευνών), Αικατερίνη Γαϊτανάκη (Καθηγήτρια)
Original Title:
Ανάλυση νέων σηματοδοτικών μονοπατιών των οπιοειδών υποδοχέων που οδηγούν σε αλλαγές της συναπτοσωμικής πλαστικότητας
Languages:
Greek
Summary:
Opioid receptors are prototypical Gi/o-coupled receptors and participate in
mechanisms controlling neural growth, differentiation and synaptic plasticity.
Previous work from our laboratory has shown that the conserved YXXL motif
within the C-terminal tail of the μ-opioid receptor (μ-OR) serves as a docking
site for STAT5A binding, with the latter being phosphorylated upon μ-OR
stimulation. Given that the δ-opioid receptor (δ-OR) contains the same
structural motif within its C-terminal tail (δ-CT), we have shown that STAT5Β
interacts also with this tetra-peptide of the δ-CT. Agonist exposure of HEK293
cells, stably expressing the flag-δ-OR, led to a G protein-dependent STAT5Β
phosphorylation mediated by c-Src kinase. Additional studies indicated that δ-
OR serves as a platform for the formation of a multi-component signaling
complex, consisting of STAT5B, c-Src kinase, Gβγ and selective Gαi/o protein
subunits. Furthermore, our findings demonstrated that δ-OR activation leads to
neuronal cell survival and neurite outgrowth via the aforementioned signaling
pathway involving Gαi/o proteins and phosphorylated STAT5B. Collectively, these
results suggest that the activation of the STAT5B-Gαi/o signaling pathway plays
a major role in δ-OR-induced neuronal cell survival and differentiation.
Keywords:
Opioid receptors, Signal Transducer and Activator of Transcription 5, G proteins, Neurite outgrowth, Signaling complex
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
407
Number of pages:
vi, 317
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