Interactions between the secreted protein Amalgam, its transmembrane receptor Neurotactin and the Abelson tyrosine kinase affect axon pathfinding.
Two novel dosage-sensitive modifiers of the Abelson tyrosine kinase (Abl) mutant phenotype have been identified. Amalgam (Ama) is a secreted protein that interacts with the transmembrane protein Neurotactin (Nrt) to promote cell:cell adhesion. We have identified an unusual missense ama allele, ama(M109), which dominantly enhances the Abl mutant phenotype, affecting axon pathfinding. Heterozygous null alleles of ama do not show this dominant enhancement, but animals homozygous mutant for both ama and Abl show abnormal axon outgrowth. Cell culture experiments demonstrate the Ama(M109) mutant protein binds to Nrt, but is defective in mediating Ama/Nrt cell adhesion. Heterozygous null alleles of nrt dominantly enhance the Abl mutant phenotype, also affecting axon pathfinding. Furthermore, we have found that all five mutations originally attributed to disabled are in fact alleles of nrt. These results suggest Ama/Nrt-mediated adhesion may be part of signaling networks involving the Abl tyrosine kinase in the growth cone.
Liebl
Eric C
EC
Department of Biology, Denison University, Granville, OH 43023, USA. liebl@denison.edu
Rowe
R Grant
RG
Forsthoefel
David J
DJ
Stammler
Amanda L
AL
Schmidt
Erica R
ER
Turski
Michelle
M
Seeger
Mark A
MA
D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion; D002490:Central Nervous System / Q000196:embryology; D003433:Crosses, Genetic; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster; D005799:Genes, Dominant; D005838:Genotype; D006720:Homozygote; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D015003:Yeasts
C476240:Ama protein, Drosophila; D029721:Drosophila Proteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C066176:Nrt protein, Drosophila; C080216:dab protein, Drosophila; D016315:Proto-Oncogene Proteins c-abl