PMID- 10391935
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, 
      a protein phosphatase-1-interacting protein.
PG  - 19894-900
AB  - Signaling through D2 class dopamine receptors is crucial to correct brain
      development and function, and dysfunction of this system is implicated in major
      neurological disorders such as Parkinson's disease and schizophrenia. To
      investigate potential novel mechanisms of D2 receptor regulation, the third
      cytoplasmic loop of the D2 dopamine receptor was used to screen a rat hippocampal
      yeast two-hybrid library. Spinophilin, a recently characterized F-actin and
      protein phosphatase-1-binding protein with a single PDZ domain was identified as 
      a protein that specifically associates with this region of D2 receptors. A direct
      interaction between spinophilin and the D2 receptor was confirmed in vitro using 
      recombinant fusion proteins. The portion of spinophilin responsible for
      interacting with the D2 third cytoplasmic loop was narrowed to a region that does
      not include the actin-binding domain, the PDZ domain, or the coiled-coil. This
      region is distinct from the site of interaction with protein phosphatase-1, and
      both D2 receptors and protein phosphatase-1 may bind spinophilin at the same
      time. The interaction is not mediated via the unique 29-amino acid insert in
      D2long; both D2long and D2short third cytoplasmic loops interact with spinophilin
      in vitro and in yeast two-hybrid assays. Expression of D2 receptors containing an
      extracellular hemagglutinin epitope in Madin-Darby canine kidney cells results in
      co-localization of receptor and endogenous spinophilin as determined by
      immunocytochemistry using antibodies directed against spinophilin and the HA tag.
      We hypothesize that spinophilin is important for establishing a signaling complex
      for dopaminergic neurotransmission through D2 receptors by linking receptors to
      downstream signaling molecules and the actin cytoskeleton.
FAU - Smith, F D
AU  - Smith FD
AD  - Department of Cell and Molecular Physiology and the Curriculum in Neurobiology,
      The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
      27599, USA.
FAU - Oxford, G S
AU  - Oxford GS
FAU - Milgram, S L
AU  - Milgram SL
LA  - eng
GR  - NS18788/NS/NINDS NIH HHS/United States
GR  - R29DK50744/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Actins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (neurabin)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Actins/metabolism
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Dogs
MH  - Gene Expression
MH  - Hippocampus/metabolism
MH  - Microfilament Proteins/*chemistry
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry
MH  - Neurons/metabolism
MH  - Phosphoprotein Phosphatases/*chemistry
MH  - Protein Binding
MH  - Protein Phosphatase 1
MH  - Rats
MH  - Receptors, Dopamine D2/*chemistry/genetics
MH  - Recombinant Fusion Proteins/chemistry
MH  - Sequence Alignment
MH  - Signal Transduction
MH  - Yeasts
EDAT- 1999/07/03 10:00
MHDA- 2000/03/11 09:00
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1074/jbc.274.28.19894 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19894-900. doi: 10.1074/jbc.274.28.19894.