Abstract
The serotonin transporter (SERT) mediates the re-uptake of released serotonin into presynaptic nerve terminals. Its activity is regulated by different mechanisms including protein kinase C (PKC) triggered internalization. Here, we used yeast 2-hybrid screening and cotransfection into 293 cells to identify a homologue of the myristoylated alanine-rich C kinase substrate (MARCKS), MacMARCKS, as a C-terminally interacting protein of SERT. Upon cotransfection with SERT, MacMARCKS caused a reduction in the maximal rate of [(3)H]serotonin uptake and reduced its down-regulation elicited by activation of PKC. Our data are consistent with MARCKS proteins regulating the plasma membrane dynamics of neurotransmitter transporters.
(c) 2002 Elsevier Science (USA).
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Blotting, Western
-
Calmodulin-Binding Proteins
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism*
-
Cell Line
-
Down-Regulation
-
Enzyme Activation / drug effects
-
Enzyme Activators / pharmacology
-
Enzyme Inhibitors / pharmacology
-
Green Fluorescent Proteins
-
Humans
-
Kidney / cytology
-
Kidney / metabolism
-
Luminescent Proteins / genetics
-
Membrane Glycoproteins / genetics
-
Membrane Glycoproteins / metabolism*
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Membrane Transport Proteins*
-
Microfilament Proteins
-
Molecular Sequence Data
-
Nerve Tissue Proteins*
-
Protein Binding / physiology
-
Protein Kinase C / metabolism
-
Protein Structure, Tertiary / physiology
-
Rats
-
Recombinant Fusion Proteins / biosynthesis
-
Recombinant Fusion Proteins / genetics
-
Sequence Homology, Amino Acid
-
Serotonin / pharmacokinetics
-
Serotonin Plasma Membrane Transport Proteins
-
Transfection
-
Two-Hybrid System Techniques
-
Vesicular Transport Proteins
Substances
-
Calmodulin-Binding Proteins
-
Carrier Proteins
-
Enzyme Activators
-
Enzyme Inhibitors
-
Luminescent Proteins
-
MARCKSL1 protein, human
-
Marcksl1 protein, rat
-
Membrane Glycoproteins
-
Membrane Proteins
-
Membrane Transport Proteins
-
Microfilament Proteins
-
Nerve Tissue Proteins
-
Recombinant Fusion Proteins
-
SLC6A4 protein, human
-
Serotonin Plasma Membrane Transport Proteins
-
Slc6a4 protein, rat
-
Vesicular Transport Proteins
-
Green Fluorescent Proteins
-
Serotonin
-
Protein Kinase C