Intracellular retention of recombinant GABAB receptors.
gamma-Aminobutyric acid type B (GABAB) receptors mediate the transmission of slow and prolonged inhibitory signals in the central nervous system. Two splice variants of GABAB receptors, GABABR1a and GABABR1b, were recently cloned from a mouse cortical and cerebellar cDNA library. As predicted, these receptors belong to the G protein-coupled receptor superfamily. We have used epitope-tagged versions of GABABR1a receptors to study the cellular distribution of these proteins in a variety of non-neuronal and neuronal cell types. Here we report that recombinant GABAB receptors fail to reach the cell surface when expressed in heterologous systems and are retained in the endoplasmic reticulum when introduced into COS cells. In addition, we prove that recombinant GABAB receptors are excluded from the cell surface when overexpressed in ganglion neurons and we further demonstrate that they fail to activate in superior cervical ganglion neurons. Together our observations suggest that recombinant GABAB receptors require additional information for functional targeting to the plasma membrane.
Medical Research Council Laboratory of Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
A
A
Couve
A K
AK
Filippov
C N
CN
Connolly
B
B
Bettler
D A
DA
Brown
S J
SJ
Moss
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D018080:Receptors, GABA-B; D011994:Recombinant Proteins