Expression of a constitutively active insulin receptor in Drosulfakinin (Dsk) neurons regulates metabolism and sleep in Drosophila

Palermo, Justin; Keene, Alex C.; DiAngelo, Justin R.

doi:10.1016/j.bbrep.2022.101280

Cited by 3 publications

(3 citation statements)

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“…D‐IR plays a crucial role in regulating growth, metabolism, and development in Drosophila 6,10,11,46,47 . Like the C. elegans counterpart, Daf‐2 , impaired D‐IR signaling is associated with extended longevity 3,6,10,48 .…”

Section: Resultsmentioning

confidence: 99%

“…D-IR plays a crucial role in regulating growth, metabolism, and development in Drosophila. 6,10,11,46,47 Like the C. elegans counterpart, Daf-2, impaired D-IR signaling is associated with extended longevity. 3,6,10,48 The R1467C (numbering according to NCBI NP_524436.2) mutation in the kinase insert region is associated with a reduction in head size, 6 body size, and a drastic increase in life expectancy of fruit flies.…”

Section: Drosophila Development and Lifespan Have Varying Effects On ...mentioning

confidence: 99%

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Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Krishnan,

Ahmed,

Hubbard

et al. 2023

The FASEB Journal

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Drosophila melanogaster (fruit fly) insulin receptor (D‐IR) is highly homologous to the human counterpart. Like the human pathway, D‐IR responds to numerous insulin‐like peptides to activate cellular signals that regulate growth, development, and lipid metabolism in fruit flies. Allelic mutations in the D‐IR kinase domain elevate life expectancy in fruit flies. We developed a robust heterologous expression system to express and purify wild‐type and longevity‐associated mutant D‐IR kinase domains to investigate enzyme kinetics and substrate specificities. D‐IR exhibits remarkable similarities to the human insulin receptor kinase domain but diverges in substrate preferences. We show that longevity‐associated mutations reduce D‐IR catalytic activity. Deletion of the unique kinase insert domain portion or mutations proximal to activating tyrosines do not influence kinase activity, suggesting their potential role in substrate recruitment and downstream signaling. Through biochemical investigations, this study enhances our comprehension of D‐IR's role in Drosophila physiology, complementing genetic studies and expanding our knowledge on the catalytic functions of this conserved signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Drosophila Development and Lifespan Have Varying Effects On ...mentioning

confidence: 99%

Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Krishnan,

Ahmed,

Hubbard

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

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“…Insulin-like peptides and elements of the insulin signaling pathway are conserved across phyla (Wu and Brown., 2006;Nassel and Broeck., 2016). The signaling pathway regulates and influences a diverse set of developmental and physiological processes including aging and sleep (Tartar et al, 2001;Broughton and Patridge., 2009;Metaxakis et al, 2014;Palermo et al, 2022;Yamaguchi et al, 2022). Unlike vertebrates which have a single insulin peptide and a family of insulin receptors (IR) and insulin-like growth factor receptors (IGFRs), Drosophila has 8 Insulin-like peptides (ILPs) and a single receptor.…”

Section: Introduction: Insulin Signalingmentioning

confidence: 99%

Neural pathways in nutrient sensing and insulin signaling

Ratnaparkhi

Sudhakaran

2022

Front. Physiol.

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Nutrient sensing and metabolic homeostasis play an important role in the proper growth and development of an organism, and also in the energy intensive process of reproduction. Signals in response to nutritional and metabolic status is received and integrated by the brain to ensure homeostasis. In Drosophila, the fat body is one of the key organs involved in energy and nutrient sensing, storage and utilization. It also relays the nutritional status of the animal to the brain, activating specific circuits which modulate the synthesis and release of insulin-like peptides to regulate metabolism. Here, we review the molecular and cellular mechanisms involved in nutrient sensing with an emphasis on the neural pathways that modulate this process and discuss some of the open questions that need to be addressed.

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