Membrane potential regulates growth: Changes in electrical potential across the plasma membrane can affect cell growth. Zhou et al. discovered that membrane potential influenced the organization of phospholipids in the membrane of cultured mammalian cells and neurons in intact flies (see the Perspective by Accardi). This in turn regulated localization and activity of the small guanine nucleotide binding protein K-Ras, an important regulator of cell proliferation. The cell membrane may thus function analogously to a field-effect transistor by adjusting the strength of mitogenic signaling. Science , this issue p. 873 ; see also p. 789

Significance: Intense insecticide usage is suggested to be a significant contributor to the observed decline of insect populations around the world. Beneficial insects play essential roles in food production and ecosystem health. It is therefore vital to understand the mechanisms by which low doses of insecticide impact insect biology in order to understand and assess the threat posed. We investigated the impacts of the neonicotinoid insecticide imidacloprid on Drosophila . The binding of the insecticide to receptors in the brain triggers oxidative stress, reduces energy levels, and induces neurodegeneration as well as vision loss. As the receptors targeted by imidacloprid are conserved among insects, and other insecticides have also been shown to cause oxidative stress, these findings have wider significance.

Objective— The present study is aimed at investigating the interaction of TRPV4 with TRPC1 and the functional role of such an interaction in flow-induced Ca ²⁺ influx. Hemodynamic blood flow is an important physiological factor that modulates vascular tone. One critical early event in this process is a cytosolic Ca ²⁺ ([Ca ²⁺ ] _i ) rise in endothelial cells in response to flow. Methods and Results— With the use of fluorescence resonance energy transfer, coimmunoprecipitation, and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a complex. In functional studies, flow elicited a transient [Ca ²⁺ ] _i increase in TRPV4-expressing human embryonic kidney (HEK) 293 cells. Coexpression of TRPC1 with TRPV4 markedly prolonged this [Ca ²⁺ ] _i transient; it also enabled this [Ca ²⁺ ] _i transient to be negatively modulated by protein kinase G. Furthermore, this flow-induced [Ca ²⁺ ] _i increase was markedly inhibited by anti–TRPC1-blocking antibody T1E3 and a dominant-negative construct TRPC1Δ567-793 in TRPV4-C1–coexpressing HEK cells and human umbilical vein endothelial cells. T1E3 also inhibited flow-induced vascular dilation in isolated rat small mesenteric artery segments. Conclusion— This study shows that TRPC1 interacts physically with TRPV4 to form a complex, and this TRPV4-C1 complex may mediate flow-induced Ca ²⁺ influx in vascular endothelial cells. The association of TRPC1 with TRPV4 prolongs the flow-induced [Ca ²⁺ ] _i transient, and it also enables this [Ca ²⁺ ] _i transient to be negatively modulated by protein kinase G. This TRPV4-C1 complex plays a key role in flow-induced endothelial Ca ²⁺ influx.