Identification of Genes That Interact With Drosophila <i>liquid facets</i>

Eun, Suk Ho; Lea, Kristi; Overstreet, Erin; Stevens, S. J. C.; Lee, Jihoon; Fischer, Janice A.

doi:10.1534/genetics.106.067959

Cited by 30 publications

(45 citation statements)

References 64 publications

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“…Recently, the endocytic protein Auxilin has been implicated in Notch signaling in Drosophila (Hagedorn et al, 2006;Eun et al, 2007). Auxilin is an adapter for the ATPase Hsc70 (Heat shock cognate 70); Auxilin binds Hsc70 with its J domain and also binds Clathrin cages, which are Hsc70 substrates.…”

Section: Introductionmentioning

confidence: 99%

Auxilin is essential for Delta signaling

2008

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Endocytosis regulates Notch signaling in both signaling and receiving cells. A puzzling observation is that endocytosis of transmembrane ligand by the signaling cells is required for Notch activation in adjacent receiving cells. A key to understanding why signaling depends on ligand endocytosis lies in identifying and understanding the functions of crucial endocytic proteins. One such protein is Epsin, an endocytic factor first identified in vertebrate cells. Here, we show in Drosophila that Auxilin, an endocytic factor that regulates Clathrin dynamics, is also essential for Notch signaling. Auxilin, a co-factor for the ATPase Hsc70, brings Hsc70 to Clathrin cages. Hsc70/Auxilin functions in vesicle scission and also in uncoating Clathrin-coated vesicles. We find that like Epsin, Auxilin is required in Notch signaling cells for ligand internalization and signaling. Results of several experiments suggest that the crucial role of Auxilin in signaling is, at least in part, the generation of free Clathrin. We discuss these observations in the light of current models for the role of Epsin in ligand endocytosis and the role of ligand endocytosis in Notch signaling.

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Section: Introductionmentioning

confidence: 99%

Auxilin is essential for Delta signaling

2008

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“…/Y males or Ral EE1 homozygous females are viable with morphological abnormalities, including reduced rough eyes, curved wings, and missing hairs and bristles (Eun et al, 2007). Ral EE1 behaves like a hypomorphic allele.…”

Section: Ee1mentioning

confidence: 99%

“…Ral EE1 behaves like a hypomorphic allele. All aspects of the Ral EE1 mutant phenotype in hemizygous males are complemented by Act5C-gal4;UAS-Ral wt (Eun et al, 2007 Fig. S1 in the supplementary material).…”

Section: Ee1mentioning

confidence: 99%

“…In Ral EE1 /Y eye discs, many ommatidia rotate either too much or too little, and R1 or R6 are frequently absent (Fig. 1E,F Ral eye defects and genetic interactions suggest that Ral regulates Notch signaling Ral EE1 was identified in a mutagenesis screen for dominant enhancers of the rough eye caused by epsin overexpression (Eun et al, 2007). Epsin is an endocytic protein required in Notch signaling cells for ligand endocytosis and signaling (Overstreet et al, 2004;Wang and Struhl, 2004;Wang and Struhl, 2005).…”

Section: Ee1mentioning

confidence: 99%

“…Epsin is an endocytic protein required in Notch signaling cells for ligand endocytosis and signaling (Overstreet et al, 2004;Wang and Struhl, 2004;Wang and Struhl, 2005). Loss-of-function alleles of genes acting in Notch signaling both positively and negatively were identified in the screen (Eun et al, 2007). To determine whether Ral plays a role in Notch signaling normally, we tested for genetic interactions between Ral and lqf loss-of-function mutations.…”

Section: Ee1mentioning

confidence: 99%

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Ral GTPase promotes asymmetric Notch activation in the Drosophila eye in response to Frizzled/PCP signaling by repressing ligand-independent receptor activation

Cho

Fischer

2011

Development

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Ral is a small Ras-like GTPase that regulates membrane trafficking and signaling. Here, we show that in response to planar cell polarity (PCP) signals, Ral modulates asymmetric Notch signaling in the Drosophila eye. Specification of the initially equivalent R3/R4 photoreceptor precursor cells in each developing ommatidium occurs in response to a gradient of Frizzled (Fz) signaling. The cell with the most Fz signal (R3) activates the Notch receptor in the adjacent cell (R4) via the ligand Delta, resulting in R3/R4 cell determination and their asymmetric positions within the ommatidium. Two mechanisms have been proposed for ensuring that the cell with the most Fz activation sends the Delta signal: Fz-dependent transcriptional upregulation in R3 of genes that promote Delta signaling, and direct blockage of Notch receptor activation in R3 by localization of an activated Fz/Disheveled protein complex to the side of the plasma membrane adjacent to R4. Here, we discover a distinct mechanism for biasing the direction of Notch signaling that depends on Ral. Using genetic experiments in vivo, we show that, in direct response to Fz signaling, Ral transcription is upregulated in R3, and Ral represses ligand-independent activation of Notch in R3. Thus, prevention of ligand-independent Notch activation is not simply a constitutive process, but is a target for regulation by Ral during cell fate specification and pattern formation.

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Intracellular trafficking in Drosophila visual system development: A basis for pattern formation through simple mechanisms

Chan

Epstein

Hiesinger

2011

Developmental Neurobiology

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Intracellular trafficking underlies cellular functions ranging from membrane remodeling to receptor activation. During multicellular organ development, these basic cell biological functions are required as both passive machinery and active signaling regulators. Exocytosis, endocytosis, and recycling of several key signaling receptors have long been known to actively regulate morphogenesis and pattern formation during Drosophila eye development. Hence, intracellular membrane trafficking not only sets the cell biological stage for receptor-mediated signaling but also actively controls signaling through spatiotemporally regulated receptor localization. In contrast to eye development, the role of intracellular trafficking for the establishment of the eye-to-brain connectivity map has only recently received more attention. It is still poorly understood how guidance receptors are spatiotemporally regulated to serve as meaningful synapse formation signals. Yet, the Drosophila visual system provides some of the most striking examples for the regulatory role of intracellular trafficking during multicellular organ development. In this review we will first highlight the experimental and conceptual advances that motivate the study of intracellular trafficking during Drosophila visual system development. We will then illuminate the development of the eye, the eye-to-brain connectivity map and the optic lobe from the perspective of cell biological dynamics. Finally, we provide a conceptual framework that seeks to explain how the interplay of simple genetically encoded intracellular trafficking events governs the seemingly complex cellular behaviors, which in turn determine the developmental product.

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Identification of Genes That Interact With Drosophila liquid facets

Cited by 30 publications

References 64 publications

Auxilin is essential for Delta signaling

Auxilin is essential for Delta signaling

Ral GTPase promotes asymmetric Notch activation in the Drosophila eye in response to Frizzled/PCP signaling by repressing ligand-independent receptor activation

Intracellular trafficking in Drosophila visual system development: A basis for pattern formation through simple mechanisms

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