title: The phosphoinositide phosphatase Sac1 is required for midline axon guidance.
abstract: Sac1 phosphoinositide (PI) phosphatases are important regulators of PtdIns(4)P turnover at the ER, Golgi, and plasma membrane (PM) and are involved in diverse cellular processes including cytoskeletal organization and vesicular trafficking. Here, we present evidence that Sac1 regulates axon guidance in the embryonic CNS of Drosophila. Sac1 is expressed on three longitudinal axon tracts that are defined by the cell adhesion molecule Fasciclin II (Fas II). Mutations in the sac1 gene cause ectopic midline crossing of Fas II-positive axon tracts. This phenotype is rescued by neuronal expression of wild-type Sac1 but not by a catalytically-inactive mutant. Finally, sac1 displays dosage-sensitive genetic interactions with mutations in the genes that encode the midline repellent Slit and its axonal receptor Robo. Taken together, our results suggest that Sac1-mediated regulation of PIs is critical for Slit/Robo-dependent axon repulsion at the CNS midline.
authors: Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
authors: Seongsoo
authors: S
authors: Lee
authors: Sungdae
authors: S
authors: Kim
authors: Minyeop
authors: M
authors: Nahm
authors: Euijae
authors: E
authors: Kim
authors: Tai-Il
authors: TI
authors: Kim
authors: Jin Ho
authors: JH
authors: Yoon
authors: Seungbok
authors: S
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000378:metabolism; D010712:Phosphatidic Acids / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D051381:Rats
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D010712:Phosphatidic Acids; C416669:Sac1 protein, mammalian; D010744:Phosphoric Monoester Hydrolases