WIDE DISTRIBUTION OF THE CYSTEINE STRING PROTEINS IN DROSOPHILA TISSUES REVEALED BY TARGETED MUTAGENESIS

The ''cysteine string protein'' (CSP) genes of higher eukaryotes code for a novel family of proteins characterized by a ''J'' domain and an unusual cysteine-rich region. Previous studies had localized the prote ins in neuropil and synaptic terminals of larval and adult Drosophila and linked the temperature-sensitive paralysis of the mutants describe d here to conditional failure of synaptic transmission. We now use the null mutants as negative controls in order to reliably detect even lo w concentrations of CSPs by immunohistochemistry, employing three mono clonal antibodies. In wild-type flies high levels of cysteine string p roteins are found not only in apparently all synaptic terminals of the embryonic, larval, and adult nervous systems, but also in the ''tall cells'' of the cardia, in the follicle cells of the ovary, in specific structures of the female spermatheca, and in the male testis and ejac ulatory bulb. In addition, low levels of CSPs appear to be present in all tissues examined, including neuronal perikarya, axons, muscles, Ma lpighian tubules, and salivary glands. Western blots of isolated tissu es demonstrate that of the four isoforms expressed in heads only the l argest is found in non-neural organs. The wide expression of CSPs sugg ests that at least some of the various phenotypes of the null mutants observed at permissive temperatures, such as delayed development, shor t adult lifespan, modified electroretinogram, and optomotor behavior, may be caused by the lack of CSPs outside synaptic terminals.