Abstract:
:The serotonin transporter (SERT) is a major regulator of serotonergic neurotransmission and anxiety-related behaviors. SERT is expressed in two alternative polyadenylation forms that differ by an evolutionarily conserved element in the 3' untranslated region of its mRNA. Expression of SERT mRNA containing the distal polyadenylation element is associated with decreased anxiety-related behaviors in mice and humans, suggesting that this element has behaviorally relevant modulatory effects on SERT expression. We have identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a protein known to integrate multiple signal transduction pathways with gene expression, as a SERT distal polyadenylation element binding protein. This interaction is functionally meaningful because genetic manipulation of hnRNPK alters expression of the SERT protein. Furthermore, the trophic factor S100β induces Src-family kinase-mediated tyrosine phosphorylation of hnRNPK and increased SERT expression. These results identify a previously unknown mechanism of regulated SERT expression and provide a putative mechanism by which the SERT distal polyadenylation element modulates anxiety-related behaviors.
journal_name
Proc Natl Acad Sci U S Aauthors
Yoon Y,McKenna MC,Rollins DA,Song M,Nuriel T,Gross SS,Xu G,Glatt CEdoi
10.1073/pnas.1301485110subject
Has Abstractpub_date
2013-07-09 00:00:00pages
11624-9issue
28eissn
0027-8424issn
1091-6490pii
1301485110journal_volume
110pub_type
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