Zn(2+) reverses functional deficits in a de novo dopamine transporter variant associated with autism spectrum disorder.
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.
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.
Peter J
PJ
Hamilton
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.
Aparna
A
Shekar
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.
Andrea N
AN
Belovich
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.
Nicole Bibus
NB
Christianson
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.
Nicholas G
NG
Campbell
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.
James S
JS
Sutcliffe
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.
Aurelio
A
Galli
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.
Heinrich Jg
HJ
Matthies
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.
Kevin
K
Erreger
Autism spectrum disorder; Dopamine; Transporter; Zinc; de novo mutation