Zn(2+) reverses functional deficits in a de novo dopamine transporter variant associated with autism spectrum disorder.

Autor:	Hamilton PJ; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Shekar A; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Belovich AN; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Christianson NB; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Campbell NG; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Sutcliffe JS; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Galli A; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Matthies HJ; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA., Erreger K; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 7124 MRB III, 465 21st Avenue S, Nashville, TN 37232 USA.; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee USA.
Jazyk:	angličtina
Zdroj:	Molecular autism [Mol Autism] 2015 Feb 24; Vol. 6, pp. 8. Date of Electronic Publication: 2015 Feb 24 (Print Publication: 2015).
DOI:	10.1186/s13229-015-0002-7
Abstrakt:	Our laboratory recently characterized a novel autism spectrum disorder (ASD)-associated de novo missense mutation in the human dopamine transporter (hDAT) gene SLC6A3 (hDAT T356M). This hDAT variant exhibits dysfunctional forward and reverse transport properties that may contribute to DA dysfunction in ASD. Here, we report that Zn(2+) reverses, at least in part, the functional deficits of ASD-associated hDAT variant T356M. These data suggest that the molecular mechanism targeted by Zn(2+) to restore partial function in hDAT T356M may be a novel therapeutic target to rescue functional deficits in hDAT variants associated with ASD.
Databáze:	MEDLINE
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