Insulin Receptor-Mediated Signaling via Phospholipase C-γ Regulates Growth and Differentiation in Drosophila

Murillo‐Maldonado, Juan Manuel; Zeineddine, Fouad Bou; Stock, Rachel; Thackeray, Justin; Riesgo-Escovar, Juan R.

doi:10.1371/journal.pone.0028067

Cited by 15 publications

(8 citation statements)

References 44 publications

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“…nub>PLCγ RNAi had similar wings to controls but were smaller ( Fig. S2), which has been reported to be caused by regulation of epidermal growth factor receptor signaling by the S2 domain of PLCγ which does not catalyze IP 3 generation (Murillo-Maldonado et al, 2011). Overall, these results show that Plc21C is the primary PLC responsible for stimulating IP 3 R in the wing disc.…”

Section: Oscillatory Ca 2+ Signal Exhibits Four Categories Of Ca 2+ Asupporting

confidence: 58%

In vivo relevance of intercellular calcium signaling inDrosophilawing development

Brodskiy

Huizar

et al. 2017

Preprint

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Recently, organ-scale intercellular Ca 2+ transients (ICTs) were reported in the Drosophila wing disc. However, the functional in vivo significance of ICTs remains largely unknown. Here we demonstrate the in vivo relevance of intercellular Ca 2+ signaling and its impact on wing development. We report that Ca 2+ signaling in vivo decreases as wing discs mature. Ca 2+ signaling ex vivo responds to fly extract in a dose-dependent manner. This suggests ICTs occur in vivo due to chemical stimulus that varies in concentration during development. RNAi mediated inhibition of genes required for ICTs results in defects in the size, shape, and vein patterning of adult wings. It also leads to reduction or elimination of in vivo Ca 2+ transients. Further, perturbations to the extracellular matrix along the basal side of the wing disc stimulates intercellular Ca 2+ waves. This is the first identified chemically defined, non-wounding stimulus of ICTs. Together, these results point toward specific in vivo functions of intercellular Ca 2+ signaling to mediate mechanical stress dissipation and ensure robust patterning during development.

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Section: Oscillatory Ca 2+ Signal Exhibits Four Categories Of Ca 2+ Asupporting

confidence: 58%

In vivo relevance of intercellular calcium signaling inDrosophilawing development

Brodskiy

Huizar

et al. 2017

Preprint

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“…In budding yeast, it has been possible to delineate this through genetic and biochemical approaches because there is a single phospholipase C gene product Plc1. Drosophila possesses three different isoforms of PLC [NorpA, Plc21C, and Small wing (Sl)] (34), and although triple-deletion mutants have not been reported in the literature, individual PLC mutants show interesting phenotypes, including small wings and rough eyes (35), similar to the zygotic ipk2 mutant defects we report. Evidence in this study hints at a different mechanism but it is also quite likely that the different PLC orthologs can compensate for each other, confounding interpretation.…”

Section: Discussionmentioning

confidence: 56%

Inositol phosphate kinase 2 is required for imaginal disc development in Drosophila

Seeds

Tsui

Sunu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Inositol phosphate kinase 2 (Ipk2), also known as IP multikinase IPMK, is an evolutionarily conserved protein that initiates production of inositol phosphate intracellular messengers (IPs), which are critical for regulating nuclear and cytoplasmic processes. Here we report that Ipk2 kinase activity is required for the development of the adult fruit fly epidermis. Ipk2 mutants show impaired development of their imaginal discs, the primordial tissues that form the adult epidermis. Although disk tissue seems to specify normally during early embryogenesis, loss of Ipk2 activity results in increased apoptosis and impairment of proliferation during larval and pupal development. The proliferation defect is in part attributed to a reduction in JAK/ STAT signaling, possibly by controlling production or secretion of the pathway's activating ligand, Unpaired. Constitutive activation of the JAK/STAT pathway downstream of Unpaired partially rescues the disk growth defects in Ipk2 mutants. Thus, IP production is essential for proliferation of the imaginal discs, in part, by regulating JAK/STAT signaling. Our work demonstrates an essential role for Ipk2 in producing inositide messengers required for imaginal disk tissue maturation and subsequent formation of adult body structures and provides molecular insights to signaling pathways involved in tissue growth and stability during development.inositol phosphates | inositol phosphate multikinase | Ipk2 | IPMK | Upd A t the confluence of numerous signaling pathways is phospholipase C (PLC)-mediated production of the second messenger inositol 1,4,5-trisphosphate (IP 3 ), a key regulator of intracellular calcium release (1). IP 3 also serves as an essential substrate for the synthesis of inositol phosphates (IPs) and pyrophosphates (PP-IPs) that are critical for eukaryotic cellular function in their own right (2-6). Phosphorylation of IP 3 by conserved inositol phosphate kinases (IPKs) leads to the synthesis of complex pools of different IP species (6). Insights into the cellular functions of IPs have been gleaned by perturbing their synthesis through genetic manipulations of the IPKs. Consequently, defects in specific cellular processes were attributed to losses of particular IPs. This revealed that IPs are specific regulators of diverse cellular processes, such as transcription, chromatin remodeling, DNA repair, RNA editing, and RNA export (3-7).An essential enzyme for the conversion of IP 3 to the array of IP and PP-IP species found in cells is the evolutionarily conserved inositol phosphate kinase 2 (Ipk2, Fig. 1A), which is also known as IP multikinase (IPMK) (4). Ipk2 was first identified in yeast as a nuclear enriched protein whose activities toward the 6-and 3-positions on the inositol ring sequentially convert IP 3 to IP 4 , and then IP 5 (Fig. 1A) (8-10). Yeast Ipk2 mutants that fail to produce IP 4 and IP 5 exhibit defects in transcriptional responses and chromatin remodeling (3). Additional "multikinase" activities described for certain Ipk2 orthologs indicate an array ...

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“…Therefore, PLC-γ functions when growth ends and differentiation begins; it also coordinates these two processes. [38] PLC-γ was the kernel node in module 10, which physically interacted with PDGFRA and upregulated CALM3, PI3K, PIB5PA, and PKC. Thus, PLC-γ is a module biomarker.…”

Section: Discussionmentioning

confidence: 99%

Identification of melanoma biomarkers based on network modules by integrating the human signaling network with microarrays

et al. 2014

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Insulin Receptor-Mediated Signaling via Phospholipase C-γ Regulates Growth and Differentiation in Drosophila

Cited by 15 publications

References 44 publications

In vivo relevance of intercellular calcium signaling inDrosophilawing development

In vivo relevance of intercellular calcium signaling inDrosophilawing development

Inositol phosphate kinase 2 is required for imaginal disc development in Drosophila

Identification of melanoma biomarkers based on network modules by integrating the human signaling network with microarrays

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