Axon Guidance

PAM May Inhibit TSC

Science's STKE  11 Jan 2005:
Vol. 2005, Issue 266, pp. tw19
DOI: 10.1126/stke.2662005tw19

D'Souza et al. report the identification of a relationship between PAM (protein associated with Myc) and tuberin, a subunit of the tuberous sclerosis complex (TSC) in axon guidance. D'Souza et al. analyzed zebrafish mutants for defects in axonal pathfinding in the retina and identified the gene esrom, encoding the zebrafish homolog of PAM. Esrom has multiple domains, including a RING finger domain, and the C-terminal portion of Esrom had autoubiquitinating activity in vitro. Esrom was present as punctate structures in retinal neurons, and retinal transplantation experiments confirmed that Esrom was required in the retinal neurons and not in the target brain region, the tectum. Analysis of the distal regions of retinal axons showed that phosphotuberin was enriched in the esr mutants--tuberin is inhibited by phosphorylation. Thus, D'Souza et al. propose that Esrom participates in a pathway involving TSC that interprets retinal growth cone cues.

J. D'Souza, M. Hendricks, S. Le Guyader, S. Subburaju, B. Grunewald, K. Scholich, S. Jesuthasan, Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc). Development 132, 247-256 (2005). [Abstract] [Full Text]