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ARF1-GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis

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dc.contributor.author Khadilkar, Rohan J.
dc.contributor.author Rodrigues, Diana
dc.contributor.author Mote, Ridim Dadasaheb
dc.contributor.author Sinha, Arghyashree Roychowdhury
dc.contributor.author Kulkarni, Vani
dc.contributor.author Magadi, Srivathsa Subramanya
dc.contributor.author Inamdar, Maneesha S.
dc.date.accessioned 2017-02-21T07:12:04Z
dc.date.available 2017-02-21T07:12:04Z
dc.date.issued 2014
dc.identifier.citation Khadilkar, RJ; Rodrigues, D; Mote, RD; Sinha, AR; Kulkarni, V; Magadi, SS; Inamdar, MS, ARF1-GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis. Proceedings of The National Academy of Sciences of The United States of America 2014, 111 (13) 4898-4903, http://dx.doi.org/10.1073/pnas.1303559111 en_US
dc.identifier.citation Proceedings of The National Academy of Sciences of The United States of America en_US
dc.identifier.citation 111 en_US
dc.identifier.citation 13 en_US
dc.identifier.issn 0027-8424
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2477
dc.description Restricted Access en_US
dc.description.abstract Drosophila melanogaster larval hematopoiesis is a well-established model to study mechanisms that regulate hematopoietic niche maintenance and control of blood cell precursor (prohemocyte) differentiation. Molecules that perturb niche function affect the balance between prohemocytes and differentiated hemocytes. The conserved hemocyte-specific endosomal protein Asrij is essential for niche function and prohemocyte maintenance. Elucidating how subcellular trafficking molecules can regulate signaling presents an important challenge. Here we show that Asrij function is mediated by the Ras family GTPase Arf79F, the Drosophila homolog of ADP ribosylation factor 1 (ARF1), essential for clathrin coat assembly, Golgi architecture, and vesicular trafficking. ARF1 is expressed in the larval lymph gland and in circulating hemocytes and interacts with Asrij. ARF1-depleted lymph glands show loss of niche cells and prohemocyte maintenance with increased differentiation. Inhibiting ARF1 activation by knocking down its guanine nucleotide exchange factor (Gartenzwerg) or overexpressing its GTPAse-activating protein showed that ARF1-GTP is essential for regulating niche size and maintaining stemness. Activated ARF1 regulates Asrij levels in blood cells thereby mediating Asrij function. Asrij controls crystal cell differentiation by affecting Notch trafficking. ARF1 perturbation also leads to aberrant Notch trafficking and the Notch intracellular domain is stalled in sorting endosomes. Thus, ARF1 can regulate Drosophila blood cell homeostasis by regulating Asrij endocytic function. ARF1 also regulates signals arising from the niche and differentiated cells by integrating the insulin-mediated and PDGF-VEGF receptor signaling pathways. We propose that the conserved ARF1-Asrij endocytic axis modulates signals that govern hematopoietic development. Thus, Asrij affords tissue-specific control of global mechanisms involved in molecular traffic. en_US
dc.description.uri http://dx.doi.org/10.1073/pnas.1303559111 en_US
dc.language.iso English en_US
dc.publisher National Academy of Sciences en_US
dc.rights @National Academy of Sciences, 2014 en_US
dc.subject Hematopoietic Progenitor Maintenance en_US
dc.subject Adp-Ribosylation Factor en_US
dc.subject Lymph Gland en_US
dc.subject Melanogaster en_US
dc.subject Protein en_US
dc.subject Activation en_US
dc.subject Networks en_US
dc.subject Steppke en_US
dc.subject Signals en_US
dc.subject Model en_US
dc.title ARF1-GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis en_US
dc.type Article en_US


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