Axons Guided by Insulin Receptor in
            <i>Drosophila</i>
            Visual System

Song, Jianbo; Wu, Lingling; Chen, Zun; Kohanski, Ronald A.; Pick, Leslie

doi:10.1126/science.1081203

Cited by 137 publications

(132 citation statements)

References 25 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…DILP release from the DILP2 neurons may thus be modulated by intracellular Ca 2ϩ signaling and function in the process of dendritic outgrowth during the pupal stages. In Drosophila, insulin signaling contributes to guidance of photoreceptor cell axons from the retina to the brain during development of the visual system (Song et al, 2003). Insulin transport into the CNS appears to increase in the neonatal period (Banks, 2004) in mammalian systems, suggesting that peripheral insulin levels influence the formation of circuits in the developing brain (Needleman and McAllister, 2008).…”

Section: Intracellular Calcium Homeostasis In Dilp2 Neurons and The Cmentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate Receptor and dSTIM Function inDrosophilaInsulin-Producing Neurons Regulates Systemic Intracellular Calcium Homeostasis and Flight

Agrawal¹,

Venkiteswaran²,

Sadaf³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

show abstract

Section: Intracellular Calcium Homeostasis In Dilp2 Neurons and The Cmentioning

confidence: 99%

Inositol 1,4,5-Trisphosphate Receptor and dSTIM Function inDrosophilaInsulin-Producing Neurons Regulates Systemic Intracellular Calcium Homeostasis and Flight

Agrawal¹,

Venkiteswaran²,

Sadaf³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The IR regulates neuronal survival in C. elegans (9). In Drosophila, the IR serves an important function to guide retinal photoreceptor axons from the retina to the brain during development (10), and the IR influences the size and number of photoreceptors (11). The lack of IR activation leads to neurodegeneration in brain/neuron-specific IR knock-out mice (12).…”

Section: Insulin Receptor (Ir)mentioning

confidence: 99%

Loss of Neuroprotective Survival Signal in Mice Lacking Insulin Receptor Gene in Rod Photoreceptor Cells

Rajala

Tanito

et al. 2008

Journal of Biological Chemistry

113

View full text Add to dashboard Cite

Insulin receptor (IR) signaling provides a trophic signal for transformed retinal neurons in culture, but the role of IR activity in vivo is unknown. We previously reported that light causes increased tyrosine phosphorylation of the IR in vivo, which leads to the downstream activation of the phosphoinositide 3-kinase and Akt pathway in rod photoreceptor cells. The functional role of IR in rod photoreceptor cells is not known. We observed that light stress induced tyrosine phosphorylation of the IR in rod photoreceptor cells, and we hypothesized that IR activation is neuroprotective. To determine whether IR has a neuroprotective role on rod photoreceptor cells, we used the Cre/lox system to specifically inactivate the IR gene in rod photoreceptors. Rodspecific IR knock-out mice have reduced the phosphoinositide 3-kinase and Akt survival signal in rod photoreceptors. The resultant mice exhibited no detectable phenotype when they were raised in dim cyclic light. However, reduced IR expression in rod photoreceptors significantly decreased retinal function and caused the loss of photoreceptors in mice exposed to bright light stress. These results indicate that reduced expression of IR in rod photoreceptor cells increases their susceptibility to lightinduced photoreceptor degeneration. These data suggest that the IR pathway is important for photoreceptor survival and that activation of the IR may be an essential element of photoreceptor neuroprotection. Insulin receptor (IR)2 signaling provides a trophic signal for transformed retinal neurons in culture (1), but the role of the IR in vivo is unknown. IR activation has been shown to rescue retinal neurons from apoptosis through a phosphoinositide 3-kinase (PI3K) cascade (1). We previously reported that light induces tyrosine phosphorylation of the retinal IR and that this activation leads to the binding of PI3K to rod outer segment (ROS) membranes (2). More recently, we demonstrated that IR activation is mediated through the G-protein-coupled receptor rhodopsin (3). IR signaling is also involved in 17␤-estradiolmediated neuroprotection in the retina (4). Recent evidence suggests a down-regulation of IR kinase activity in diabetic retinopathy that is associated with the deregulation of downstream signaling molecules (5). Deletion of several downstream effector molecules of the IR signaling pathway, such as IRS-2 (6), Akt2 (7), and Bcl-xl (8), in the retina resulted in a photoreceptor degeneration phenotype. These studies clearly indicate the importance of the IR signaling pathway in the retina.The IR is highly conserved, and the high degree of IR signaling homology between Caenorhabditis elegans, Drosophila, and humans suggests functional conservation in mammalian retina. The IR regulates neuronal survival in C. elegans (9). In Drosophila, the IR serves an important function to guide retinal photoreceptor axons from the retina to the brain during development (10), and the IR influences the size and number of photoreceptors (11). The lack of IR activation leads to neurod...

show abstract

“…[1][2][3][4] However, excessive insulin signaling caused by hyperinsulinemia or overexpression of insulin receptor (IR) has been linked to cancer progression. 5 Recent epidemiological and experimental studies have demonstrated that hyperinsulinemia is a major cancer risk factor among many type 2 diabetes mellitus patients and obese individuals.…”

Section: Introductionmentioning

confidence: 99%

Insulin activates the insulin receptor to downregulate the PTEN tumour suppressor

et al. 2013

View full text Add to dashboard Cite

Insulin and insulin-like growth factor-1 signaling have fundamental roles in energy metabolism, growth and development. Recent research suggests hyperactive insulin receptor (IR) and hyperinsulinemia are cancer risk factors. However, the mechanisms that account for the link between the hyperactive insulin signaling and cancer risk are not well understood. Here we show that an insulin-like signaling inhibits the DAF-18/(phosphatase and tensin homolog) PTEN tumour suppressor in Caenorhabditis elegans and that this regulation is conserved in human breast cancer cells. We show that inhibiting the IR increases PTEN protein levels, while increasing insulin signaling decreases PTEN protein levels. Our results show that the kinase region of IRb subunit physically binds to PTEN and phosphorylates on Y27 and Y174. Our genetic results also show that DAF-2/IR negatively regulates DAF-18/PTEN during C. elegans axon guidance. As PTEN is an important tumour suppressor, our results therefore suggest a possible mechanism for increased cancer risk observed in hyperinsulinemia and hyperactive IR individuals.

show abstract

Axons Guided by Insulin Receptor in Drosophila Visual System

Cited by 137 publications

References 25 publications

Inositol 1,4,5-Trisphosphate Receptor and dSTIM Function inDrosophilaInsulin-Producing Neurons Regulates Systemic Intracellular Calcium Homeostasis and Flight

Inositol 1,4,5-Trisphosphate Receptor and dSTIM Function inDrosophilaInsulin-Producing Neurons Regulates Systemic Intracellular Calcium Homeostasis and Flight

Loss of Neuroprotective Survival Signal in Mice Lacking Insulin Receptor Gene in Rod Photoreceptor Cells

Insulin activates the insulin receptor to downregulate the PTEN tumour suppressor

Contact Info

Product

Resources

About