ABSTRACT
The control of growth is fundamental to the developing metazoan. Here, we show that CHICO, a Drosophila homolog of vertebrate IRS1-4, plays an essential role in the control of cell size and growth. Animals mutant for chico are less than half the size of wild-type flies, owing to fewer and smaller cells. In mosaic animals, chico homozygous cells grow slower than their heterozygous siblings, show an autonomous reduction in cell size, and form organs of reduced size. Although chico flies are smaller, they show an almost 2-fold increase in lipid levels. The similarities of the growth defects caused by mutations in chico and the insulin receptor gene in Drosophila and by perturbations of the insulin/IGF1 signaling pathway in vertebrates suggest that this pathway plays a conserved role in the regulation of overall growth by controling cell size, cell number, and metabolism.
Subject(s)
Carrier Proteins , Drosophila Proteins , Insect Proteins/metabolism , Intracellular Signaling Peptides and Proteins , Receptor, Insulin/metabolism , Amino Acid Sequence , Animals , Apoptosis , Body Constitution , Cell Count , Cell Size , Drosophila/genetics , Drosophila/metabolism , Drosophila/physiology , Female , Insect Proteins/genetics , Insulin Receptor Substrate Proteins , Lipid Metabolism , Male , Molecular Sequence Data , Mutagenesis , Phosphatidylinositol 3-Kinases/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Receptor, Insulin/genetics , Sequence Homology, Amino Acid , VertebratesABSTRACT
The known roles for calcium-binding proteins in developmental signaling pathways are reviewed. Current information on the calcium-binding characteristics of three classes of cell-surface developmental signaling proteins (EGF-domain proteins, cadherins and integrins) is presented together with an overview of the intracellular pathways downstream of these surface receptors. The developmental roles delineated to date for the universal intracellular calcium sensor, calmodulin, and its targets, and for calcium-binding regulators of the cytoskeleton are also reviewed.
Subject(s)
Calcium-Binding Proteins/chemistry , Calcium-Binding Proteins/metabolism , Embryonic Induction/physiology , Embryonic and Fetal Development/physiology , Signal Transduction/physiology , Animals , Cadherins/chemistry , Cadherins/metabolism , Drosophila , Epidermal Growth Factor/chemistry , Humans , Integrins/chemistry , Integrins/physiology , Models, Molecular , Protein ConformationABSTRACT
The regulatory protein calmodulin is a major mediator of calcium-induced changes in cellular activity. To analyze the roles of calmodulin in an intact animal, we have generated a calmodulin null mutation in Drosophila melanogaster. Maternal calmodulin supports calmodulin null individuals throughout embryogenesis, but they die within 2 days of hatching as first instar larvae. We have detected two pronounced behavioral abnormalities specific to the loss of calmodulin in these larvae. Swinging of the head and anterior body, which occurs in the presence of food, is three times more frequent in the null animals. More strikingly, most locomotion in calmodulin null larvae is spontaneous backward movement. This is in marked contrast to the wild-type situation where backward locomotion is seen only as a stimulus-elicited avoidance response. Our finding of spontaneous avoidance behavior has striking similarities to the enhanced avoidance responses produced by some calmodulin mutations in Paramecium. Thus our results suggest evolutionary conservation of a role for calmodulin in membrane excitability and linked behavioral responses.
