Molecular characterisation of two structurally distinct groups of human homers, generated by extensive alternative splicing.
Homer proteins bind specifically to the C termini of the metabotropic glutamate receptor mGluR1alpha/a and mGluR5, play a role in their targeting and modulate their synaptic properties. We have discovered that extensive alternative splicing generates a family of 17 Homer proteins. These fall into two distinct groups of 12 "long" Homers, which all have a coiled-coil domain at their C termini, and five "short" Homers, which lack such a domain. All Homers contain the N-terminal sequence responsible for their binding to mGluR1alpha/a receptors and can be co-localised with the recombinantly expressed mGluR1alpha/a protein in HEK-293 cells. The existence of the long and the short variants of each of the Homer-1, Homer-2 and Homer-3 proteins reflects the fundamental principles of Homer functions.
Soloviev
M M
MM
Medical Research Council Anatomical Neuropharmacology Unit, Mansfield Road, Oxford, OX1 3TH, UK. mikhail.soloviev@pharm.ox.ac.uk
Ciruela
F
F
Chan
W Y
WY
McIlhinney
R A
RA
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D014644:Genetic Variation / Q000235:genetics; D006367:HeLa Cells; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C104077:metabotropic glutamate receptor type 1