Interactions between the secreted protein Amalgam, its transmembrane receptor Neurotactin and the Abelson tyrosine kinase affect axon pathfinding

• Published in: Development (Cambridge) Vol. 130; no. 14; pp. 3217 - 3226
• Main Authors: Liebl, Eric C, Rowe, R Grant, Forsthoefel, David J, Stammler, Amanda L, Schmidt, Erica R, Turski, Michelle, Seeger, Mark A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15-07-2003
• Subjects: Alleles; Animals; Axons - metabolism; Axons - physiology; Cell Adhesion; Central Nervous System - embryology; Crosses, Genetic; Drosophila; Drosophila melanogaster; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; Genes, Dominant; Genotype; Homozygote; Immunoglobulins - chemistry; Immunoglobulins - metabolism; Membrane Glycoproteins - metabolism; Models, Genetic; Mutation; Mutation, Missense; Nerve Tissue Proteins - genetics; Neurons - cytology; Neurons - metabolism; Phenotype; Proto-Oncogene Proteins c-abl - metabolism; RNA Interference; Signal Transduction; Yeasts
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.00545

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.