The Sac1 Lipid Phosphatase Regulates Cell Shape Change and the JNK Cascade during Dorsal Closure in Drosophila

Wei, Ho-Chun; Sanny, Justina; Shu, Huidy; Baillie, David L.; Brill, Julie A.; Price, James V.; Harden, Nicholas

doi:10.1016/j.cub.2003.09.056

Cited by 35 publications

(40 citation statements)

References 20 publications

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“…Subsequently, Sac1p, an essential gene in yeast, has been shown to regulate PI(4)P levels and to play important roles in the Golgi apparatus, actin cytoskeleton dynamics, and other cellular functions (Hughes et al, 2000;Foti et al, 2001). Studies in Drosophila melanogaster have shown that mutation of Sac1 results in disruption of JNK mitogen-activated protein kinase signaling, resulting in embryo lethality (Wei et al, 2003). It is intriguing that, in plants, the rhd4-1 null allele has defective root hairs but no other observed morphological defects.…”

Section: Discussionmentioning

confidence: 99%

ROOT HAIR DEFECTIVE4Encodes a Phosphatidylinositol-4-Phosphate Phosphatase Required for Proper Root Hair Development inArabidopsis thaliana

et al. 2008

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Polarized expansion of root hair cells in Arabidopsis thaliana is improperly controlled in root hair-defective rhd4-1 mutant plants, resulting in root hairs that are shorter and randomly form bulges along their length. Using time-lapse fluorescence microscopy in rhd4-1 root hairs, we analyzed membrane dynamics after labeling with RabA4b, a marker for polarized membrane trafficking in root hairs. This revealed stochastic loss and recovery of the RabA4b compartment in the tips of growing root hairs, consistent with a role for the RHD4 protein in regulation of polarized membrane trafficking in these cells. The wildtype RHD4 gene was identified by map-based cloning and was found to encode a Sac1p-like phosphoinositide phosphatase. RHD4 displayed a preference for phosphatidylinositol-4-phosphate [PI(4)P] in vitro, and rhd4-1 roots accumulated higher levels of PI(4)P in vivo. In wild-type root hairs, PI(4)P accumulated primarily in a tip-localized plasma membrane domain, but in rhd4-1 mutants, significant levels of PI(4)P were detected associated with internal membranes. A fluorescent RHD4 fusion protein localized to membranes at the tips of growing root hairs. We propose that RHD4 is selectively recruited to RabA4b-labeled membranes that are involved in polarized expansion of root hair cells and that, in conjunction with the phosphoinositide kinase PI-4Kb1, RHD4 regulates the accumulation of PI(4)P on membrane compartments at the tips of growing root hairs.

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Section: Discussionmentioning

confidence: 99%

ROOT HAIR DEFECTIVE4Encodes a Phosphatidylinositol-4-Phosphate Phosphatase Required for Proper Root Hair Development inArabidopsis thaliana

et al. 2008

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“…All of these defects can be rescued by overexpression of Sac1, and both its catalytic activity and ability to cycle between the ER and the Golgi were required for complementation (929). Sac1 mutant flies also die in embryonic stage and develop dorsal closure defects (1689). The structure of yeast Sac1 has been recently solved at 2 Å resolution.…”

Section: R(t/s) Motif Within Their Catalytic Domains (Figure 8bmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,365

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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“…For example, mutations affecting the Drosophila PtdIns(4)P 5-kinase Skittles (Sktl) are lethal and clones of sktl mutant cells are largely inviable, making it difficult to assess PtdIns(4,5)P 2 function in vivo (Hassan et al, 1998). Similarly, the PtdIns 4-phosphatase Sac1 is essential, limiting analysis of the consequences of PtdIns(4)P overproduction (Wei et al, 2003). In the course of studies examining PtdIns(4,5)P 2 function in Drosophila male-germ-cell cytokinesis, we depleted plasma membrane PtdIns(4,5)P 2 by targeted expression of a lipid phosphatase (Wong et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis

Wei

Rollins

Fabian

et al. 2008

Journal of Cell Science

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Axonemes are microtubule-based organelles of crucial importance in the structure and function of eukaryotic cilia and flagella. Despite great progress in understanding how axonemes are assembled, the signals that initiate axoneme outgrowth remain unknown. Here, we identified phosphatidylinositol phosphates (phosphoinositides) as key regulators of early stages of axoneme outgrowth in Drosophila melanogaster spermatogenesis. In a study of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] function in developing Drosophila male germ cells, we depleted PtdIns(4,5)P2 by expression of a potent phosphoinositide phosphatase. Phosphatase expression dramatically inhibited sperm tail formation and perturbed microtubule organization in a manner reversible by co-expression of a PtdIns 4-phosphate 5-kinase. Depletion of PtdIns(4,5)P2 caused increased levels of basal body γ-tubulin and altered the distribution of proteins known to be required for axoneme assembly. Examination of PtdIns(4,5)P2-depleted spermatids by transmission electron microscopy revealed defects in basal body docking to the nuclear envelope, and in axoneme architecture and integrity of the developing flagellar axoneme and axial sheath. Our results provide the first evidence that phosphoinositides act at several steps during flagellar biogenesis, coordinately regulating microtubule and membrane organization. They further suggest that phosphoinositides play evolutionarily conserved roles in flagella and cilia, across phyla and in structurally diverse cell types.

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The Sac1 Lipid Phosphatase Regulates Cell Shape Change and the JNK Cascade during Dorsal Closure in Drosophila

Cited by 35 publications

References 20 publications

ROOT HAIR DEFECTIVE4Encodes a Phosphatidylinositol-4-Phosphate Phosphatase Required for Proper Root Hair Development inArabidopsis thaliana

ROOT HAIR DEFECTIVE4Encodes a Phosphatidylinositol-4-Phosphate Phosphatase Required for Proper Root Hair Development inArabidopsis thaliana

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis

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