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 Zn(2+)-finger domain, central PDZ and C(2)A domains, and a C-terminal C(2)B domain; RIM2beta consists of a short beta-specific sequence followed by central PDZ and C(2)A domains and a C-terminal C(2)B domain; and RIM2gamma, 3gamma, and 4gamma consist of only a C(2)B domain. In the RIM2 gene, RIM2beta and 2gamma are transcribed from internal promoters. alpha- and beta-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.
Wang
Yun
Y
Center for Basic Neuroscience, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75390, USA.
Südhof
Thomas C
TC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins; D020440:Gene Duplication; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013569:Synapses / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; C107293:Rim protein, mammalian; D019204:GTP-Binding Proteins