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Substrate‐mediated enhancement of phosphorylated tyrosine hydroxylase in nigrostriatal dopamine neurons: evidence for a role of α‐synuclein
Author(s) -
Drolet Robert E.,
Behrouz Bahareh,
Lookingland Keith J.,
Goudreau John L.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03606.x
Subject(s) - tyrosine hydroxylase , phosphorylation , raclopride , tyrosine phosphorylation , dopamine , medicine , biology , tyrosine , endocrinology , nigrostriatal pathway , serine , knockout mouse , chemistry , microbiology and biotechnology , biochemistry , receptor , dopamine receptor , dopaminergic , substantia nigra
Tyrosine hydroxylase (TH) protein, phosphorylated at serine‐40, serine‐31 and serine‐19, and enzyme catalytic activity were compared under basal conditions and in activated nigrostriatal dopamine (NSDA) neurons of wild‐type and homozygous α‐synuclein knockout mice. Mice were injected with the D2 antagonist raclopride to stimulate NSDA neuronal activity in the presence or absence of supplemental l ‐tyrosine. There was no difference in phosphorylated TH levels or TH catalytic activity between wild‐type and α‐synuclein knockout mice under basal conditions or following raclopride‐induced acceleration of NSDA activity. In wild‐type animals, tyrosine administration potentiated the raclopride‐induced increase in phosphorylated TH and enzyme activity. However, tyrosine administration did not enhance phosphorylated TH levels or enzyme catalytic activity in raclopride‐stimulated NSDA neurons in α‐synuclein knockout mice. These findings suggest that α‐synuclein plays a role in the ability of tyrosine to either enhance TH phosphorylation or hinder TH inactivation during accelerated neuronal activity. The present study supports the hypothesis that α‐synuclein functions as a molecular chaperone protein that regulates the phosphorylation state of TH in a substrate and activity‐dependent manner.