Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc).
Visual system development is dependent on correct interpretation of cues that direct growth cone migration and axon branching. Mutations in the zebrafish esrom gene disrupt bundling and targeting of retinal axons, and also cause ectopic arborization. By positional cloning, we establish that esrom encodes a very large protein orthologous to PAM (protein associated with Myc)/Highwire/RPM-1. Unlike motoneurons in Drosophila highwire mutants, retinal axons in esrom mutants do not arborize excessively, indicating that Esrom has different functions in the vertebrate visual system. We show here that Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. These data identify a mediator of signal transduction in retinal growth cones, which is required for topographic map formation.
D'Souza
Jasmine
J
Developmental Neurobiology Group, Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Rep. of Singapore.
Hendricks
Michael
M
Le Guyader
Sylvie
S
Subburaju
Sivan
S
Grunewald
Barbara
B
Scholich
Klaus
K
Jesuthasan
Suresh
S
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004330:Drosophila; D005123:Eye / Q000196:embryology*; D005838:Genotype; D020439:Growth Cones / Q000378:metabolism*; D017403:In Situ Hybridization; D008024:Ligands; D008856:Microscopy, Fluorescence; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D008957:Models, Genetic; D010641:Phenotype; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D008024:Ligands; D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C497200:mycbp2 protein, zebrafish; D012313:RNA; D006899:Mixed Function Oxygenases; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases