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PLA2 and secondary metabolites of arachidonic acid control filopodial behavior in neuronal growth cones.

机译:PLA2和花生四烯酸的次生代谢产物控制神经元生长锥中的丝虫行为。

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摘要

The neuronal growth cone provides the sensory and motor structure that guides neuronal processes to their target. The ability of a growth cone to navigate correctly depends on its filopodia, which sample the environment by continually extending and retracting as the growth cone advances. Several second messengers systems that are activated upon contact with extracellular cues have been reported to affect growth cone morphology by changing the length and number of filopodia. Because recent studies have suggested that guidance cues can signal via G-protein coupled receptors to regulate phospholipases, we here investigated whether phospholipase A(2) (PLA(2)) may control filopodial dynamics and could thereby affect neuronal pathfinding. Employing identified Helisoma neurons in vitro, we demonstrate that inhibition of PLA(2) with 2 microM BPB caused a 40.3% increase in average filopodial length, as well as a 37.3% reduction in the number of filopodia on a growth cone. The effect of PLA(2) inhibition on filopodial length was mimicked by the inhibition of G-proteins with 500 ng/ml pertussis toxin and was partially blocked by the simultaneous activation of PLA(2) with 50 nM melittin. We provide evidence that PLA(2) acts via production of arachidonic acid (AA), because (1) the effect of inhibition of PLA(2) could be counteracted by supplying AA exogenously, and (2) the inhibition of cyclooxygenase, which metabolizes AA into prostaglandins, also increased filopodial length. We conclude that filopodial contact with extracellular signals that alter the activity of PLA(2) can control growth cone morphology and may affect neuronal pathfinding by regulating the sensory radius of navigating growth cones. Cell Motil. Cytoskeleton 57:53-67, 2004.
机译:神经元生长锥提供将神经元过程引导至其目标的感觉和运动结构。生长锥正确导航的能力取决于它的丝状伪足,该丝状伪足通过随着生长锥前进而不断延伸和缩回来采样环境。据报道,与细胞外线索接触后被激活的多个第二信使系统会通过改变丝状伪足的长度和数量来影响生长锥的形态。因为最近的研究表明指导提示可以通过G蛋白偶联受体信号调节磷脂酶,所以我们在这里研究了磷脂酶A(2)(PLA(2))是否可以控制丝虫动力学并因此可以影响神经寻路。在体外采用已鉴定的Helisoma神经元,我们证明用2 microM BPB抑制PLA(2)导致平均丝虫长度增加40.3%,以及在生长锥上减少丝虫病数量37.3%。 PLA(2)对丝状体长度的抑制作用是通过抑制500 ng / ml百日咳毒素的G蛋白来模拟的,而通过同时激活50 nM蜂毒肽对PLA(2)的作用而部分阻止。我们提供的证据表明PLA(2)通过生产花生四烯酸(AA)起作用,因为(1)外源供应AA可以抵消PLA(2)的抑制作用,以及(2)代谢的环氧合酶的抑制作用AA进入前列腺素,也增加了丝虫长度。我们得出的结论是,与改变PLA(2)活性的细胞外信号进行丝足接触可以控制生长锥的形态,并可能通过调节导航生长锥的感觉半径来影响神经元寻路。细胞动力。细胞骨架57:53-67,2004。

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