生物谷報(bào)道：最新一期Cell以特色文章刊登血腦屏障研究領(lǐng)域的最重大的進(jìn)展。來(lái)自于加州大學(xué)的科學(xué)家Gaul發(fā)現(xiàn)了GPCR信號(hào)通路在果蠅的血腦屏障的形成中起到關(guān)鍵性作用,，這一研究為揭示更高等的生物的血腦屏障發(fā)育的機(jī)理,，以及為研制突破血腦屏障的藥物的機(jī)制提供重要的研究基礎(chǔ),。
The blood-brain barrier of Drosophila is established by surface glia, which ensheath the nerve cord and insulate it against the potassium-rich hemolymph by forming intercellular septate junctions. The mechanisms underlying the formation of this barrier remain obscure. Here, we show that the G protein-coupled receptor (GPCR) Moody, the G protein subunits Gαi and Gαo, and the regulator of G protein signaling Loco are required in the surface glia to achieve effective insulation. Our data suggest that the four proteins act in a complex common pathway. At the cellular level, the components function by regulating the cortical actin and thereby stabilizing the extended morphology of the surface glia, which in turn is necessary for the formation of septate junctions of sufficient length to achieve proper sealing of the nerve cord. Our study demonstrates the importance of morphogenetic regulation in blood-brain barrier development and places GPCR signaling at its core.
Figure 3. Colocalization and Physical Interaction of G Protein Signaling Components
(A–C) Projections of confocal stacks (5–7.5 μm) from third-instar larvae, ventral surface views.
(A) Moody (magenta) and Loco (green) antibody stainings of fixed tissue. (B) Live imaging of Moody-RFP (magenta) and Loco-GFP (green) driven by the surface-glial-specific moody-Gal4. Moody is found predominantly at the plasma membrane; visible are the cell boundaries between the surface glia (arrows), as well as surface glial extensions into the paracellular space between underlying neuronal cell bodies (arrowheads; inset). Loco is more broadly distributed within the cell but strongly colocalizes with Moody at the plasma membrane.
(C) Moody protein (magenta) colocalizes with the SJ marker Nrg-GFP (green).
(D and E) Gi or Go (magenta) and Loco-GFP (driven by moody-Gal4; green) antibody stainings of fixed larval tissue, showing coexpression in the surface glia; single confocal sections, lateral view.
(F) Transiently transfected S2 cells expressing Loco-GFP (driven by actin-Gal4; green) alone or together with different Gα subunits (magenta). Loco-GFP by itself localizes to cytoplasm/nucleus. In the presence of Gi or Go, but not Gs, it relocalizes to cytoplasm/plasma membrane.
原文來(lái)源：
Schwabe et al. GPCR Signaling Is Required for Blood-Brain Barrier Formation in Drosophila Cell, Vol 123, 133-144, 7 October 2005
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