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Dopamine receptor interacting proteins: unraveling the receptor signalplex
Author(s) -
Hazelwood Lisa A,
Free R Benjamin,
Cabrera David M,
Sibley David R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.726.3
Subject(s) - receptor , internalization , microbiology and biotechnology , colocalization , g protein coupled receptor , chemistry , function (biology) , cytosol , biology , biochemistry , enzyme
Dopamine receptors (DARs) are known to exist as constituents of a large macromolecular complex of interacting proteins, termed the signalplex. These interacting proteins may be transmembrane or cytosolic, and can play a variety of roles in receptor trafficking, function or desensitization. To identify interacting partners, we have employed a co‐immunoprecipitation assay for D 1 and D 2 DARs from both mouse brain and transfected cell lines. When coupled with mass spectrometry (MS) sequencing, these experiments have allowed detection and subsequent peptide‐matching to more than 50 proteins within a non‐redundant protein database. Among the novel interacting proteins identified through these experiments were various subunits of the Na + ,K + ‐ATPase (NKA) and the regulatory protein sorting nexin 25 (SNX25). Studies have revealed multiple isoforms of SNX25 that influence DAR expression and function, possibly via sorting or internalization of the receptors. Experiments with the NKA have shown that the DARs and NKA can reciprocally regulate one another, providing a control mechanism for both receptor signaling and cellular ion balance. These data offer insights into the cellular components of the DAR signalplex, and indicate that interacting proteins can influence the DARs at various stages of receptor processing and function. LAH and RBF contributed equally to this work. Support Contributed By: NINDS/NIH and the NIGMS PRAT Program (LAH)