phalloidine and Abnormalities--Multiple

Lipid modification of proteins by the addition of myristic acid to the N-terminal is important in a number of critical cellular processes, for example, signal transduction and the modulation of membrane association by myristoyl switches. Myristic acid is added to proteins by the enzyme N-myristoyltransferase (NMT) and in this paper we detail the effects on embryonic development of a null mutation in the Drosophila NMT gene. Mutant embryos display a range of phenotypes, including failures of head involution, dorsal closure, and germ-band retraction, morphogenetic processes that require cellular movements. Embryos with milder phenotypes have more specific defects in the central nervous system, including thinning of the ventral nerve chord and, in some embryos, specific scission at parasegment 10. Staining of mutant embryos with phalloidin shows that the mutant embryos have a disrupted actin cytoskeleton and abnormal cell morphology. These phenotypes are strikingly similar to those caused by genes involved in dynamic rearrangement of the actin cytoskeleton. For example the myristoylated nonreceptor tyrosine kinases Dsrc42A and Dsrc64B were shown recently to be key regulators of dorsal closure. In addition, analysis of cell death reveals widespread ectopic apoptosis. Our findings are consistent with the hypothesis that the myristoyl switches and signaling pathways characterized at the biochemical level have important functions in fundamental morphogenetic processes.

Topics: Abnormalities, Multiple; Actins; Acyltransferases; Amino Acid Sequence; Animals; Apoptosis; Base Sequence; Cell Death; Cytoskeleton; DNA Transposable Elements; Drosophila; Embryo, Nonmammalian; Genes, Lethal; Mutation; Nervous System Malformations; Phalloidine; Phenotype; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Signal Transduction