Genomic definition of RIM proteins:: evolutionary amplification of a family of synaptic regulatory proteins

RIMS are synaptic proteins that are essential for normal neurotransmitter release. We now show that while invertebrates contain only a single RIM gene, vertebrates contain four: two large genes encoding RIM1alpha (0.50 Mb) or RIM2alpha, 2beta, and 2gamma (0.50-0.75 Mb) and two smaller genes encoding RIM3gamma (14 kb) or RIM4gamma (55 kb). RIM1alpha and RIM2alpha consist of an N-terminal Zn2+-finger domain, central PDZ and C(2)A domains, and a C-terminal C2B domain; RIM2beta consists of a short beta-specific sequence followed by central PDZ and C(2)A domains and a C-terminal C2B domain; and RIM2gamma, 3gamma, and 4gamma consist of only a C2B domain. In the RIM2 gene, RIM2beta and 2gamma are transcribed from internal promoters. alpha- and alpha-RIMS are extensively alternatively spliced at three canonical positions, resulting in >200 variants that differ by up to 400 residues. Thus gene duplication, alternative splicing, and multiple promoters diversify a single invertebrate RIM into a large vertebrate protein family. The multiplicity of vertebrate RIMS may serve to fine-tune neurotransmitter release beyond a fundamental, evolutionarily conserved, and common function for RIMS. (C) 2003 Elsevier Science (USA). All rights reserved.