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Cited 22 time in webofscience Cited 25 time in scopus
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SNX14 is a bifunctional negative regulator for neuronal 5-HT6 receptor signaling

Authors
Ha, Chang ManPark, DaehunKim, YoonjuNa, MyeongsuPanda, SurabhiWon, SehoonKim, HyunRyu, HoonPark, Zee YongRasenick, Mark M.Chang, Sunghoe
Issue Date
May-2015
Publisher
COMPANY OF BIOLOGISTS LTD
Keywords
SNX14; G protein-coupled receptor; Regulator of G protein signaling; Sorting nexin; Guanosine triphosphatase-activating proteins; 5-hydroxytryptamine type 6 receptor; 5-HT
Citation
JOURNAL OF CELL SCIENCE, v.128, no.9, pp.1848 - 1861
Journal Title
JOURNAL OF CELL SCIENCE
Volume
128
Number
9
Start Page
1848
End Page
1861
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/878
DOI
10.1242/jcs.169581
ISSN
0021-9533
Abstract
The 5-hydroxytryptamine (5-HT, also known as serotonin) subtype 6 receptor (5-HT6R, also known as HTR6) plays roles in cognition, anxiety and learning and memory disorders, yet new details concerning its regulation remain poorly understood. In this study, we found that 5-HT6R directly interacted with SNX14 and that this interaction dramatically increased internalization and degradation of 5-HT6R. Knockdown of endogenous SNX14 had the opposite effect. SNX14 is highly expressed in the brain and contains a putative regulator of G-protein signaling (RGS) domain. Although its RGS domain was found to be non-functional as a GTPase activator for Gas, we found that it specifically bound to and sequestered Gas, thus inhibiting downstream cAMP production. We further found that protein kinase A (PKA)-mediated phosphorylation of SNX14 inhibited its binding to Gas and diverted SNX14 from Gas binding to 5-HT6R binding, thus facilitating the endocytic degradation of the receptor. Therefore, our results suggest that SNX14 is a dual endogenous negative regulator in 5-HT6R-mediated signaling pathway, modulating both signaling and trafficking of 5-HT6R.
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