Molecular determinants of metabotropic glutamate receptor 1B trafficking.
The metabotropic glutamate receptor mGluR1 undergoes alternative splicing to generate isoforms differing in C-terminal sequence. The mechanism by which these isoforms give different functional responses to agonists in vitro is so far unclear. Using the native mGluR1 and CD2-mGluR1 chimeric molecules, as well as their C-terminal truncations and mutants, we identified an endoplasmic reticulum (ER) retention signal Arg-Arg-Lys-Lys within the C-terminal sequence of mGluR1b. Its presence results in a much reduced cell surface expression of the receptor and chimeric molecules in cell lines and their restricted trafficking in neurones. This motif is also present in the C-terminus of mGluR1a, but its effect is overcome by a region of the mGluR1a-specific C-terminal sequence (amino acids 975-1098). Our results indicate that these splice variants of mGluR1 utilize different targeting pathways and suggest that this may be a general phenomenon in the metabotropic glutamate receptor gene family.
Medical Research Council Anatomical Neuropharmacology Unit, Oxford, OX1 3TH, United Kingdom.
W Y
WY
Chan
M M
MM
Soloviev
F
F
Ciruela
R A
RA
McIlhinney
D000595:Amino Acid Sequence; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry / Q000235:genetics; D019556:COS Cells; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018801:CD2 Antigens; D021382:Protein Sorting Signals; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C104077:metabotropic glutamate receptor type 1