Alternative splicing of the Drosophila PTEN gene

Smith, Anna; Smith, Alice; Alrubaie, Saif; Coehlo, Carmen; Leevers, Sally J.; Ashworth, Alan

doi:10.1016/s0167-4781(99)00172-4

Cited by 15 publications

(13 citation statements)

References 23 publications

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“…3B). Intriguingly, apical enrichment of PTEN2 depends on the PDZ-binding motif, as the PTEN3 protein, which lacks the PDZ binding motif but is otherwise identical to PTEN2 (Smith et al, 1999), was present on the whole plasma membrane and in the cytoplasm (Fig. 3C).…”

Section: Bazooka Colocalizes With Pten In Epithelia and Neuroblastsmentioning

confidence: 98%

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Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling

et al. 2005

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Cell polarity in Drosophila epithelia, oocytes and neuroblasts is controlled by the evolutionarily conserved PAR/aPKC complex, which consists of the serine-threonine protein kinase aPKC and the PDZ-domain proteins Bazooka(Baz) and PAR-6. The PAR/aPKC complex is required for the separation of apical and basolateral plasma membrane domains, for the asymmetric localization of cell fate determinants and for the proper orientation of the mitotic spindle. How the complex exerts these different functions is not known. We show that the lipid phosphatase PTEN directly binds to Baz in vitro and in vivo, and colocalizes with Baz in the apical cortex of epithelia and neuroblasts. PTEN is an important regulator of phosphoinositide turnover that antagonizes the activity of PI3-kinase. We show that Pten mutant ovaries and embryos lacking maternal and zygotic Pten function display phenotypes consistent with a function for PTEN in the organization of the actin cytoskeleton. In freshly laid eggs, the germ plasm determinants oskarmRNA and Vasa are not localized properly to the posterior cytocortex and pole cells do not form. In addition, the actin-dependent posterior movement of nuclei during early cleavage divisions does not occur and the synchrony of nuclear divisions at syncytial blastoderm stages is lost. Pten mutant embryos also show severe defects during cellularization. Our data provide evidence for a link between the PAR/aPKC complex, the actin cytoskeleton and PI3-kinase signaling mediated by PTEN.

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Section: Bazooka Colocalizes With Pten In Epithelia and Neuroblastsmentioning

confidence: 98%

“…1A). All three clones contain a canonical PDZ-binding motif at the very C terminus (STYL) (Songyang et al, 1997) and correspond to splice form 2 of PTEN (PTEN2) (Smith et al, 1999). The PDZbinding motif is essential for interaction with the PDZ domains of Baz.…”

Section: Bazooka Binds To Ptenmentioning

confidence: 99%

Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling

et al. 2005

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“…PI3K, c-Akt and PTEN are involved in a very ancient signaling system, and are highly conserved proteins among organisms as diverse as amoeba Dictyostelium discoideum, platyhelminthes (planarian Schmidtea mediterranea; trematode Schistosoma mansoni), nematodes (C. elegans), and vertebrates [67][68][69][70][71][72][73]. The PTEN gene is conserved in the invertebrate D. melanogaster and undergoes alternative RNA splicing [74] (Fig. 3).…”

Section: Evolution Of Primary Signaling Events In Vegf-regulated Physmentioning

confidence: 99%

Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System

Ponnambalam

Alberghina

2011

Mol Neurobiol

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The vascular network is closely linked to the neural system, and an interdependence is displayed in healthy and in pathophysiological responses. How has close apposition of two such functionally different systems occurred? Here, we present a hypothesis for the evolution of the vascular network from an ancestral neural guidance system. Biological cornerstones of this hypothesis are the vascular endothelial growth factor (VEGF) protein family and cognate receptors. The primary sequences of such proteins are conserved from invertebrates, such as worms and flies that lack discernible vascular systems compared to mammals, but all these systems have sophisticated neuronal wiring involving such molecules. Ancestral VEGFs and receptors (VEGFRs) could have been used to develop and maintain the nervous system in primitive eukaryotes. During evolution, the demands of increased morphological complexity required systems for transporting molecules and cells, i.e., biological conductive tubes. We propose that the VEGF-VEGFR axis was subverted by evolution to mediate the formation of biological tubes necessary for transport of fluids, e.g., blood. Increasingly, there is evidence that aberrant VEGF-mediated responses are also linked to neuronal dysfunctions ranging from motor neuron disease, stroke, Parkinson's disease, Alzheimer's disease, ischemic brain disease, epilepsy, multiple sclerosis, and neuronal repair after injury, as well as common vascular diseases (e.g., retinal disease). Manipulation and correction of the VEGF response in different neural tissues could be an effective strategy to treat different neurological diseases.

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“…PTEN is alternatively spliced and has three and six isoforms in D. melanogaster [38] and the mosquito Aedes aegypti , respectively [39]. In mosquitoes, isoforms show developmental- and tissue-specific mRNA levels [39].…”

Section: Introductionmentioning

confidence: 99%

Honey Bee PTEN – Description, Developmental Knockdown, and Tissue-Specific Expression of Splice-Variants Correlated with Alternative Social Phenotypes

et al. 2011

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BackgroundPhosphatase and TENsin (PTEN) homolog is a negative regulator that takes part in IIS (insulin/insulin-like signaling) and Egfr (epidermal growth factor receptor) activation in Drosophila melanogaster. IIS and Egfr signaling events are also involved in the developmental process of queen and worker differentiation in honey bees (Apis mellifera). Here, we characterized the bee PTEN gene homologue for the first time and begin to explore its potential function during bee development and adult life.ResultsHoney bee PTEN is alternatively spliced, resulting in three splice variants. Next, we show that the expression of PTEN can be down-regulated by RNA interference (RNAi) in the larval stage, when female caste fate is determined. Relative to controls, we observed that RNAi efficacy is dependent on the amount of PTEN dsRNA that is delivered to larvae. For larvae fed queen or worker diets containing a high amount of PTEN dsRNA, PTEN knockdown was significant at a whole-body level but lethal. A lower dosage did not result in a significant gene down-regulation. Finally, we compared same-aged adult workers with different behavior: nursing vs. foraging. We show that between nurses and foragers, PTEN isoforms were differentially expressed within brain, ovary and fat body tissues. All isoforms were expressed at higher levels in the brain and ovaries of the foragers. In fat body, isoform B was expressed at higher level in the nurse bees.ConclusionOur results suggest that PTEN plays a central role during growth and development in queen- and worker-destined honey bees. In adult workers, moreover, tissue-specific patterns of PTEN isoform expression are correlated with differences in complex division of labor between same-aged individuals. Therefore, we propose that knowledge on the roles of IIS and Egfr activity in developmental and behavioral control may increase through studies of how PTEN functions can impact bee social phenotypes.

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Alternative splicing of the Drosophila PTEN gene

Cited by 15 publications

References 23 publications

Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling

Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling

Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System

Honey Bee PTEN – Description, Developmental Knockdown, and Tissue-Specific Expression of Splice-Variants Correlated with Alternative Social Phenotypes

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