Multidisciplinary studies have led to the discovery and characterization of cysteine string proteins (csps) in both Drosophila and Torpedo. Phenotypic analysis of csp mutants in Drosophila demonstrates a crucial role for csp in synaptic transmission. Expression studies of Torpedo csp (Tcsp) in Xenopus oocytes suggests that the protein has some role in the function of presynaptic Ca2+ channels. However, biochemical purification of Tcsp indicates that is associated with synaptic vesicles rather than with the plasma membrane of presynaptic terminals where Ca2+ (...) channels reside. These results suggest a model in which csps serve as a link by which docked synaptic vesicles could modulate the activity of presynaptic Ca2+ channels. (shrink)

Ion channels play key roles in the generation and propagation of nerve impulses by mediating ionic fluxes across excitable membranes. Elucidation of the structure and function of these proteins is a major goal in understanding the molecular mechanisms of membrane excitability. Much work has focused on sodium channels, whose activity is of primary importance in producing nerve impulses. Despite the recent cloning and sequencing of a sodium channel structural gene, many unanswered questions remain. To address some of these question genetically, (...) Drosophila mutants with altered sodium channels are being isolated and subjected to multidisciplinary analyses. Ultimately, these can provide novel approaches for understanding the function and regulation of sodium channels at a molecular level. (shrink)

Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to induced dysfunction of SD+ spermatids. Since its discovery in 1956, SD and its mode of action have baffled biologists. Recently, substantial progress has been made in elucidating this puzzle. Sd, the primary gene responsible for distortion encodes a mutant RanGAP, a key protein in the Ran signaling pathway required for nuclear transport and other nuclear functions. The mutant (...) protein is enzymatically active but mislocalized to nuclei, which apparently disrupts Ran signaling by reducing intranuclear Ran‐GTP levels. Some evidence suggests that a defect in nuclear transport may be the main cause of sperm dysfunction. Although important questions remain, the basic mechanism of distortion is now understood sufficiently well that specific hypotheses can be formulated and tested. This previously mysterious genetic system may now offer unique insights into novel aspects of regulation by Ran. BioEssays 25:108–115, 2003. © 2003 Wiley Periodicals, Inc. (shrink)