Heptaspanning membrane receptors and cytoskeletal/scaffolding proteins: focus on adenosine, dopamine, and metabotropic glutamate receptor function.
Most cellular functions are mediated by multiprotein complexes. In neurons, these complexes are directly involved in the proper neuronal transmission, which is responsible for phenomena like learning, memory, and development. In recent years studies based on two-hybrid screens and proteomic, biochemical, and cell biology approaches have shown that intracellular domains of G protein-coupled receptors (GPCRs) or heptaspanning membrane receptors (HSMRs) interact with intracellular proteins. These interactions are the basis of a protein network associated with these receptors, which includes scaffolding proteins containing one or several PDZ (postsynaptic-density-95/discs-large/zona occludens-1) domains, signaling proteins, and proteins of the cytoskeleton. The present article is focused on the emerging evidence for interactions of adenosine, dopamine, and metabotropic glutamate receptors, with scaffolding and cytoskeletal proteins that play a role in the targeting and anchoring of these receptors to the plasma membrane, thus contributing to neuronal development and plasticity. Finally, given the complexity of neurological disorders such as ischemic stroke, Alzheimer's disease, and epilepsy, exploitation of these HSMR-associated interactions might prove to be efficient in the treatment of such disorders.
Ciruela
Francisco
F
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, 08028 Barcelona, Spain. fciruela@ub.edu
Canela
Laia
L
Burgueño
Javier
J
Soriguera
Ana
A
Cabello
Nuria
N
Canela
Enric I
EI
Casadó
Vicent
V
Cortés
Antonio
A
Mallol
Josefa
J
Woods
Amina S
AS
Ferré
Sergi
S
Lluis
Carmen
C
Franco
Rafael
R
D000818:Animals; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011954:Receptors, Dopamine / Q000737:chemistry / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000502:physiology*
D046911:Macromolecular Substances; D011954:Receptors, Dopamine; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1