Interaction of the C-terminal region of the rat serotonin transporter with MacMARCKS modulates 5-HT uptake regulation by protein kinase C

Biochem Biophys Res Commun. 2002 Jun 7;294(2):272-9. doi: 10.1016/S0006-291X(02)00460-6.

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.

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

Associated data

  • GENBANK/AJ301677