title: The F-actin-microtubule crosslinker Shot is a platform for Krasavietz-mediated translational regulation of midline axon repulsion.
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 eIF2beta 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.
authors.affiliation: Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Lee
authors.forename: Minyeop
authors.initials: M
authors.lastname: Nahm
authors.forename: Mihye
authors.initials: M
authors.lastname: Lee
authors.forename: Minjae
authors.initials: M
authors.lastname: Kwon
authors.forename: Euijae
authors.initials: E
authors.lastname: Kim
authors.forename: Alireza Dehghani
authors.initials: AD
authors.lastname: Zadeh
authors.forename: Hanwei
authors.initials: H
authors.lastname: Cao
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
authors.forename: Jeongbin
authors.initials: J
authors.lastname: Yim
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kolodziej
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism / Q000821:virology; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D040061:Eukaryotic Initiation Factor-5 / Q000235:genetics / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D029721:Drosophila Proteins; D040061:Eukaryotic Initiation Factor-5; D039642:Eukaryotic Initiation Factors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C520428:Krasavietz protein, Drosophila; C450828:shot protein, Drosophila