Cellular
Compartmentalization of Dopamine Receptors
The cell membrane is a barrier that
encloses the cell and is composed of a lipid bilayer. Associated
with the bilayer are numerous proteins and according to classical models
these proteins are free to randomly diffuse and interact, like floating
objects in the ocean. However, we have used a novel technique to
show that the D2 receptor (D2R) for the neurotransmitter, dopamine, is
compartmentalized in the cell membrane and in addition, that D2R-binding
drugs can disrupt D2R cell membrane compartmentalization. D2R is a
major target of drugs used to treat both schizophrenia and Parkinson's
disease but the cellular mechanisms for supression of disease symptoms
are not known. We hypothesize that drug-induced disruption of D2R
compartmentalization can alter D2R-mediated cellular signals and is
important in the clinical actions of D2R-targeting drugs. The project
will attempt to identify the cellular pickets and fences responsible for
compartmentalizing D2R in the cell membrane.
