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Phosphatidylinositol (4,5)‐bisphosphate regulates psychostimulant behaviors via a membrane protein interaction (358.1)
Author(s) -
Galli Aurelio
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.358.1
Subject(s) - chemistry , dopamine transporter , amphetamine , drosophila melanogaster , transporter , microbiology and biotechnology , phosphatidylinositol 4,5 bisphosphate , dopamine , biophysics , phosphatidylinositol , biochemistry , biology , neuroscience , signal transduction , gene
Phosphatidylinositol (4,5)‐bisphosphate (PIP 2 ) tightly regulates the function of ion channels and ion transporters. The human dopamine (DA) transporter (hDAT) is a key regulator of DA homeostasis and is a target of the psychostimulant amphetamine (AMPH). Here, we demonstrate that PIP 2 interacts electrostatically with specific hDAT positively charged residues and that this direct electrostatic interaction facilitates AMPH‐induced, DAT‐mediated DA efflux and the psychomotor properties of AMPH. Substitution of these residues with uncharged amino acids reduces hDAT‐PIP 2 interactions and AMPH‐induced DA efflux, without altering hDAT physiological function, DA uptake. We evaluated, for the first time, the significance of this interaction in vivo using locomotion as a behavioral assay in Drosophila melanogaster . Expression of mutated hDAT with reduced PIP 2 interaction in DA Drosophila neurons impairs AMPH‐induced locomotion without altering basal locomotion. We present the first demonstration of how PIP 2 interactions with a membrane protein regulate organismal behaviors, such as locomotion.