Band 4.1 proteins are expressed in the retina and interact with both isoforms of the metabotropic glutamate receptor type 8.
The function of the CNS depends on the correct regulation of neurotransmitter receptors by interacting proteins. Here, we screened a retinal cDNA library for proteins interacting with the intracellular C-terminus of the metabotropic glutamate receptor isoform 8a (mGluR8a). The band 4.1B protein binds to the C-termini of mGluR8a and mGluR8b, co-localizes with these glutamate receptors in transfected mammalian cells, facilitates their cell surface expression and inhibits the mGluR8 mediated reduction of intracellular cAMP concentrations. In contrast, no interaction with 4.1B was observed for other mGluRs tested. Amino acids encoded by exons 19 and 20 of 4.1B and a stretch of four basic amino acids present in the mGluR8 C-termini mediate the protein interaction. Besides binding to 4.1B, mGluR8 isoforms interact with 4.1G, 4.1N, and 4.1R. Because band 4.1 transcripts undergo extensive alternative splicing, we analyzed the splicing pattern of interacting regions and detected a 4.1B isoform expressed specifically in the retina. Within this tissue, mGluR8 and 4.1B, 4.1G, 4.1N, and 4.1R show a comparable distribution, being expressed in both synaptic layers and in somata of the ganglion cell layer. In summary, our studies identified band 4.1 proteins as new players for the mGluR8 mediated signal transduction.
Rose
Melanie
M
Institut für Biochemie (Emil-Fischer-Zentrum), Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Dütting
Eva
E
Enz
Ralf
R
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D018094:Receptors, Metabotropic Glutamate; C028841:erythrocyte membrane band 4.1 protein; C111435:metabotropic glutamate receptor 8