<i>Drosophila</i> Past1 is involved in endocytosis and is required for germline development and survival of the adult fly

Olswang-Kutz, Yael; Gertel, Yaron; Benjamin, Sigi; Sela, Orly; Pekar, Olga; Arama, Eli; Steller, Hermann; Horowitz, Mia; Segal, Daniel

doi:10.1242/jcs.054080

Cited by 6 publications

(14 citation statements)

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“…10). We speculate that Eps15 is involved because of the three EH-domain proteins in Drosophila (Eps15, Dap160, Past1), none have Clathrin binding motifs, and Eps15 is the only one with motifs for a known Clathrin-binding protein (AP-2) (Koh et al, 2007; Olswang-Kutz et al, 2008). From analysis of mutant phenotypes and genetic interaction studies, there is no evidence for the involvement of Eps15 nor AP-2 in Notch signaling (Gonzalez-Gaitan and Jackle, 1997; Koh et al, 2007; Windler and Bilder, 2010).…”

Section: Discussionmentioning

confidence: 99%

Drosophila Epsin's role in Notch ligand cells requires three Epsin protein functions: The lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules

Xie

Cho

Fischer

2012

Developmental Biology

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Epsin is an endocytic protein that binds Clathrin, the plasma membrane, Ubiquitin, and also a variety of other endocytic proteins through well-characterized motifs. Although Epsin is a general endocytic factor, genetic analysis in Drosophila and mice revealed that Epsin is essential specifically for internalization of ubiquitinated transmembrane ligands of the Notch receptor, a process required for Notch activation. Epsin’s mechanism of function is complex and context-dependent. Consequently, how Epsin promotes ligand endocytosis and thus Notch signaling is unclear, as is why Notch signaling is uniquely dependent on Epsin. Here, by generating Drosophila lines containing transgenes that express a variety of different Epsin deletion and substitution variants, we tested each of the five protein or lipid interaction modules for a role in Notch activation by each of the two ligands, Serrate and Delta. There are five main results of this work that impact present thinking about the role of Epsin in ligand cells. First, we discovered that deletion or mutation of both UIMs destroyed Epsin’s function in Notch signaling and had a greater negative impact on Epsin activity than removal of any other module type. Second, only one of Epsin’s two UIMs was essential. Third, the lipid-binding function of the ENTH domain was required only for maximal Epsin activity. Fourth, although the C-terminal Epsin modules that interact with Clathrin, the adapter protein complex AP-2, or endocytic accessory proteins were necessary collectively for Epsin activity, their functions were highly redundant; most unexpected was the finding that Epsin’s Clathrin binding motifs were dispensable. Finally, we found that signaling from either ligand, Serrate or Delta, required the same Epsin modules. All of these observations are consistent with a model where Epsin’s essential function in ligand cells is to link ubiquitinated Notch ligands to Clathrin-coated vesicles through other Clathrin adapter proteins. We propose that Epsin’s specificity for Notch signaling simply reflects its unique ability to interact with the plasma membrane, Ubiquitin, and proteins that bind Clathrin.

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Section: Discussionmentioning

confidence: 99%

Drosophila Epsin's role in Notch ligand cells requires three Epsin protein functions: The lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules

Xie

Cho

Fischer

2012

Developmental Biology

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“…In parallel with the initial functional studies in mammalian cells [12], the single Caenorhabditis elegans orthologue of human EHD1, known as Rme-1, was demonstrated to control the recycling of internalized receptors from the endocytic recycling compartment to the plasma membrane [63], entirely consistent with subsequent in vitro studies. In Drosophila melanogaster , another invertebrate sytem in which there is also a single EHD orthologue (known as Past1), deletion of the gene leads to the premature death of adult flies and their infertility [64]. In addition, Garland cells derived from flies lacking Past1 display aberrant endocytosis [64].…”

Section: Introductionmentioning

confidence: 99%

“…In Drosophila melanogaster , another invertebrate sytem in which there is also a single EHD orthologue (known as Past1), deletion of the gene leads to the premature death of adult flies and their infertility [64]. In addition, Garland cells derived from flies lacking Past1 display aberrant endocytosis [64]. The original study describing EHD1 knock-down in mice did not discern any phenotype, suggesting a high level of functional redundancy between the EHD paralogues [30]; however mouse embryonic fibroblasts derived from these animals did display delayed receptor recycling [14, 30] and decreased levels of cellular cholesterol [25].…”

Section: Introductionmentioning

confidence: 99%

EHD proteins: key conductors of endocytic transport

Naslavsky

Caplan

2011

Trends in Cell Biology

211

254

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Regulation of endocytic transport is controlled by an elaborate network of proteins. Rab GTP-binding proteins and their effectors have well-defined roles in mediating specific endocytic transport steps, but until recently, less was known about the four mammalian dynamin-like C-terminal Eps15 Homology Domain (EHD) proteins that also regulate endocytic events. In recent years, however, great strides have been made in understanding the structure and function of these unique proteins. Indeed, a growing body of literature addresses EHD protein structure, interactions with binding partners, functions in mammalian cells, and the generation of various new model systems. Accordingly, this is now an opportune time to pause and review the function and mechanisms of action of EHD proteins, and to highlight some of the challenges and future directions for the field.

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“…Similarly, some markers are expressed in cells across multiple timepoints, thus marking a single cell type in several clusters. For example, Past1, which encodes a plasma membrane protein known to interact with Notch, marks the stretched cell lineage in clusters 24, 25, and 26 [72]. Altogether, we were able to assign cell type identities for all clusters and identified 6,296 genes that show significant expression in different clusters.…”

Section: Scrna-seq Identifies Unique Cell Clusters and Markers To Assmentioning

confidence: 81%

Single-cell RNA sequencing of adultDrosophilaovary identifies transcriptional programs governing oogenesis

Jevitt¹,

Chatterjee²,

Xie³

et al. 2019

Preprint

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Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modelled extensively using the Drosophila ovary. While different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic dataset for the adult Drosophila ovary and connected tissues. This dataset captures the entire transcriptional trajectory of the developing follicle cell population over time. Our findings provide detailed insight into processes such as cell-cycle switching, migration, symmetry breaking, nurse cell engulfment, egg-shell formation, and signaling during corpus luteum formation, marking a newly identified oogenesis-to-ovulation transition. Altogether, these findings provide a broad perspective on oogenesis at a single-cell resolution while revealing new genetic markers and fate-specific transcriptional signatures to facilitate future studies.

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Drosophila Past1 is involved in endocytosis and is required for germline development and survival of the adult fly

Cited by 6 publications

References 0 publications

Drosophila Epsin's role in Notch ligand cells requires three Epsin protein functions: The lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules

Drosophila Epsin's role in Notch ligand cells requires three Epsin protein functions: The lipid binding function of the ENTH domain, a single Ubiquitin interaction motif, and a subset of the C-terminal protein binding modules

EHD proteins: key conductors of endocytic transport

Single-cell RNA sequencing of adultDrosophilaovary identifies transcriptional programs governing oogenesis

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