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 gluta mate receptor mGIuR1 alpha/a and mGluR5, play a role in their targeting and modulate their synaptic properties. We have discovered that extensive alte rnative splicing generates a family of 17 Homer proteins. These fall into t wo distinct groups of 12 "long" Homers, which all have a coiled-coil domain at their C termini, and five "short" Horners, which lack such a domain. Al l Horners contain the N-terminal sequence responsible for their binding to mGluR1 alpha/a receptors and can be co-localised with the recombinantly exp ressed mGluR1 alpha/a protein in HEK-293 cells. The existence of the long a nd the short variants of each of the Homer-1, Homer-2 and Homer-3 proteins reflects the fundamental principles of Homer functions. (C) 2000 Academic P ress.