Retrograde flow rate is increased in growth cones from myosin IIB knockout mice
Retrograde flow rate is increased in growth cones from myosin IIB knockout mice
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DOI：
10.1242/jcs.00335
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发表时间：
2003-03-15
影响因子：
4
通讯作者：
Bridgman, PC
中科院分区：
文献类型：
--
作者：
Brown, ME;Bridgman, PC
肌球蛋白IIB基因敲除小鼠的生长锥具有降低的生长速率和牵引力。生长锥的牵引力、逆向流动和向前推进之间有着密切的关系。所有这三种活动似乎至少部分依赖肌球蛋白。因此，我们现在已经测试了肌球蛋白IIB基因敲除小鼠和正常同窝出生小鼠的生长锥之间的逆行流速差异。通过将神经生长因子包被的二氧化硅珠用激光镊子放在生长锥的表面上，或者通过跟踪GFP-肌球蛋白IIA斑点，我们发现与野生型相比，敲除生长锥的逆行流速增加了两倍多。这些数据表明，肌球蛋白IIA和IIB通常有助于逆行流动和流动的性质是强烈的肌球蛋白IIB的影响，因为它的位置和丰度。然而，在缺乏肌球蛋白IIB的情况下，肌球蛋白IIA接管了这一功能。逆行流速的变化可能反映了这两种肌球蛋白功能特性的差异。敲除生长锥还表现出片状伪足稳定性降低，这可能是逆行流速增加的部分结果。此外，微管穿透较短的距离进入丝状伪足，这表明流速的增加可能会对微管依赖的丝状伪足成熟产生不利影响。总之，这些数据支持的想法，向前推进的生长锥是肌球蛋白II依赖，并涉及多种肌球蛋白II亚型。
Growth cones of myosin-IIB-knockout mice have reduced outgrowth rates and traction force. There is a close relationship between traction force, retrograde flow and forward advance of growth cones. All three activities appear to be at least partially myosin dependent. Therefore, we have now tested for differences in retrograde flow rates between growth cones from myosin-IIB-knockout mice and their normal littermates. By placing nerve-growth-factor-coated silica beads on the surface of growth cones with laser tweezers, or by tracking GFP-myosin IIA spots, we found that the retrograde flow rate was increased more than two fold in the knockout growth cones compared with the wild type. These data suggest that both myosin IIA and IIB normally contribute to retrograde flow and the properties of the flow are strongly influenced by myosin IIB because of its location and abundance. However, in the absence of myosin IIB, myosin IIA takes over this function. The change in retrograde flow rate may reflect the difference in functional properties of these two myosins. Knockout growth cones also exhibited reduced stability of lamellipodia, possibly as a partial consequence of this increased retrograde flow rate. In addition, microtubules penetrated a shorter distance into filopodia, which suggests that the increase in flow rate may adversely affect the microtubule-dependent maturation of filopodia. Taken together these data support the idea that the forward advance of the growth cone is myosin II dependent and involves multiple myosin II isoforms.