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Varghese, J.

Publications and source records attributed to Varghese, J..

2 recordsLinked to original sources

Insulin signalling activates multiple feedback loops to elicit hunger-induced feeding in Drosophila

Insulin, a highly conserved peptide hormone, links nutrient availability to metabolism and growth in animals. Besides this, in fed states insulin levels are high and insulin acts as a satiety hormone. In animals that are food deprived insulin levels remain low which facilitates hunger induced feeding. Contrary to expectations, we present evidence for persistent Drosophila insulin-like peptide gene expression and insulin signalling during initial phases of starvation. Maintenance of insulin signalling is crucial to sustain feeding responses during initial stages of starvation. Insulin signalling acts in a feedback loop involving the abdominal fatbody to maintain dilp gene expression in the early stages of food deprivation. Furthermore, another feedback regulatory loop between insulin-producing cells (IPCs) and neurons that produce the orectic hormone short-neuropeptide-F (sNPF), maintains sNPF levels and triggers feeding behavior. Thus, insulin acts through multiple feedback regulatory loops to elicit orexigenic responses and aid in efficient utilization of energy stores during early starvation.

developmental biology

FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Our previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.\n\nSummary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

cell biology