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The F-actin-microtubule crosslinker Shot is a platform for Krasavietz-mediated translational regulation of midline axon repulsion.

Cited 51 time in Web of Science Cited 51 time in Scopus
Authors
Lee, Seungbok; Lee, Seongsoo; Nahm, Minyeop; Lee, Mihye; Kwon, Minjae; Kim, Euijae; Zadeh, Alireza Dehghani; Cao, Hanwei; Kim, Hyung-Jun; Lee, Zang Hee; Oh, Seog Bae; Yim, Jeongbin; Kolodziej, Peter A
Issue Date
2007-05
Publisher
Company of Biologists
Citation
Development 134, 1767-1777
Abstract
Axon extension and guidance require a coordinated assembly of F-actin and microtubules as well as regulated translation. The molecular basis of how the translation of mRNAs encoding guidance proteins could be closely tied to the pace of cytoskeletal assembly is poorly understood. Previous studies have shown that the F-actin-microtubule crosslinker Short stop (Shot) is required for motor and sensory axon extension in the Drosophila embryo. Here, we provide biochemical and genetic evidence that Shot functions with a novel translation inhibitor, Krasavietz (Kra, Exba), to steer longitudinally directed CNS axons away from the midline. Kra binds directly to the C-terminus of Shot, and this interaction is required for the activity of Shot to support midline axon repulsion. shot and kra mutations lead to weak robo-like phenotypes, and synergistically affect midline avoidance of CNS axons. We also show that shot and kra dominantly enhance the frequency of midline crossovers in embryos heterozygous for slit or robo, and that in kra mutant embryos, some Robo-positive axons ectopically cross the midline that normally expresses the repellent Slit. Finally, we demonstrate that Kra also interacts with the translation initiation factor eIF2β and inhibits translation in vitro. Together, these data suggest that Kra-mediated translational regulation plays important roles in midline axon repulsion and that Shot functions as a direct physical link between translational regulation and cytoskeleton reorganization.
ISSN
0950-1991
Language
English
URI
https://hdl.handle.net/10371/68965
DOI
https://doi.org/10.1242/dev.02842
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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