Constitutive endocytosis of the metabotropic glutamate receptor mGluR7 is clathrin-independent.
Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs) that are widely expressed throughout the brain and are involved in synaptic development, transmission, and plasticity. The endocytosis of several members of the GPCR superfamily of receptors, such as beta-adrenergic receptors, has been studied extensively. In contrast, the mechanisms regulating mGluR endocytosis and intracellular trafficking remain poorly defined. We describe here for the first time a distinct endocytic and intracellular sorting pathway utilized by mGluR7. We show that mGluR7 constitutively internalizes via a non-clathrin mediated pathway in heterologous cells and in neurons. Unlike clathrin-mediated NMDAR endocytosis, mGluR7 traffics via an Arf6-positive endosomal pathway, similar to other well-characterized proteins such as major histocompatibility complex class I (MHC I) and the GPI-anchored protein CD59. Thus constitutive endocytosis of mGluR7 in neurons is not regulated by clathrin-dependent mechanisms, and this clathrin-independent pathway ultimately determines the amount of receptor present on the plasma membrane available to bind and respond to glutamate.
Lavezzari
Gabriela
G
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 2C903, Bethesda, MD 20892, USA.
Roche
Katherine W
KW
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000818:Animals; D002478:Cells, Cultured; D002966:Clathrin / Q000502:physiology*; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011992:Endosomes; D005455:Fluorescent Antibody Technique / Q000379:methods; D006624:Hippocampus / Q000166:cytology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014168:Transferrin / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D002966:Clathrin; D015395:Histocompatibility Antigens Class I; D018094:Receptors, Metabotropic Glutamate; D014168:Transferrin; D019014:fas Receptor; C102719:metabotropic glutamate receptor 7; D013395:Sucrose; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715349:Arf6 protein, rat