The soluble NSF attachment proteins (SNAPs) enable N-ethyl-maleimide-sensitive fusion protein (NSF) to bind to target membranes. Here we report the cloning and sequencing of complementary DNAs encoding alpha-, beta- and gamma-SNAPs. Two of these proteins, alpha and gamma, are found in a wide range of tissues, and act synergistically in intra-Golgi transport. The third, beta, is a brain-specific isoform of alpha-SNAP. Thus, NSF and SNAPs appear to be general components of the intracellular membrane fusion apparatus, and their action at specific sites of fusion must be controlled by SNAP receptors particular to the membranes being fused, as described in the accompanying article.
The detection and discrimination of odorants in mammals is thought to be mediated by a family of 100-1000 seven transmembrane domain receptor proteins, although none of these putative olfactory receptors have been shown to bind individual odorants with high affinity. We have used a genetic approach to identify the genomic regions responsible for the differential ability of two inbred mouse strains to detect a single odorant, isovaleric acid. Results obtained with a behavioral assay were consistent with a limited number of genes conferring the ability to detect isovaleric acid. One genetic location mapped to a 0.3 cM region between D4MIT37 and D4MIT156 on mouse chromosome 4. A second locus mapped to the distal end of mouse chromosome 6. The most likely cause of the behavior difference between the two strains of mice is the loss of the receptor protein or proteins responsible for recognizing isovaleric acid. High resolution genetic mapping provides a novel approach to the identification of genes critical for the detection of particular odorants.
Our understanding of olfaction has progressed rapidly in recent years as a result of the molecular genetic approaches being used to study this sensory system in a variety of model organisms. Considerable success has been achieved in identifying proteins of the mammalian signaling system that are analogous to those present in other sensory systems. More recently, genetic selection of mutations that cause defects in olfactory function in Drosophila melanogaster and Caenorhabditis elegans has led to the identification of additional proteins that play a role in the detection of odorants. The application of genetic, electrophysiological, and molecular analyses to olfactory function in mammals is also shedding light on the mechanisms that account for sensitivity and specificity in this system.
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