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Mol. Cells 2011; 32(5): 477-482

Published online October 21, 2011

https://doi.org/10.1007/s10059-011-0168-6

© The Korean Society for Molecular and Cellular Biology

The Phosphoinositide Phosphatase Sac1 Is Required for Midline Axon Guidance

Seongsoo Lee1,5, Sungdae Kim2,5, Minyeop Nahm1, Euijae Kim1, Tai-Il Kim3, Jin Ho Yoon4, and Seungbok Lee1,2,*

1Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 2Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul 151-742, Korea, 3Department of Periodontology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 4Basic Science Research Institute, School of Biological Science and Chemistry, Sungshin Women’s University, Seoul 142-732, Korea, 5These authors contributed equally to this work.

Correspondence to : *Correspondence: seunglee@snu.ac.kr

Received: August 16, 2011; Accepted: August 29, 2011

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.

Keywords Drosophila, midline axon guidance, phosphoinositide phosphatase, Sac1

Article

Research Article

Mol. Cells 2011; 32(5): 477-482

Published online November 30, 2011 https://doi.org/10.1007/s10059-011-0168-6

Copyright © The Korean Society for Molecular and Cellular Biology.

The Phosphoinositide Phosphatase Sac1 Is Required for Midline Axon Guidance

Seongsoo Lee1,5, Sungdae Kim2,5, Minyeop Nahm1, Euijae Kim1, Tai-Il Kim3, Jin Ho Yoon4, and Seungbok Lee1,2,*

1Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 2Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul 151-742, Korea, 3Department of Periodontology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 4Basic Science Research Institute, School of Biological Science and Chemistry, Sungshin Women’s University, Seoul 142-732, Korea, 5These authors contributed equally to this work.

Correspondence to:*Correspondence: seunglee@snu.ac.kr

Received: August 16, 2011; Accepted: August 29, 2011

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.

Keywords: Drosophila, midline axon guidance, phosphoinositide phosphatase, Sac1

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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