Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in dendrites of hippocampal neurons

Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in dendrites of hippocampal neurons
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DOI:
10.1242/jcs.00854
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发表时间:
2004-01-15
影响因子:
4
通讯作者:
Mikoshiba, K
Mikoshiba, K
中科院分区:
生物学2区
文献类型:
--
作者:
Bannai, H;Inoue, T;Mikoshiba, K

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尽管内质网(endoplasmic reticulum,ER)通过胞内Ca ~(2+)通道释放的Ca ~(2+)在神经元的各种活动中发挥着重要作用,但ER在神经元树突中的准确分布和动态变化仍不清楚。为了阐明这些,我们在培养的小鼠海马神经元中表达荧光蛋白标记的ER蛋白,并使用延时显微镜监测它们的运动。我们在这里报告,一个子室的ER形式在相对较大的囊泡,能够,类似于网状ER,吸收和释放Ca 2+。ER的囊泡亚隔室以0.2-0.3 μ m/秒的速度在顺行和逆行方向上沿树突沿着快速移动。微管的耗竭、显性负性驱动蛋白的过表达和反义DNA的耗竭均降低了运动囊泡的数量和速度,表明驱动蛋白可能驱动ER囊泡亚室沿树突中的微管沿着运输。ER的Ca 2 +-可释放的亚隔室的快速运输可能有助于将新鲜ER蛋白快速供应到树突的远端部分,或有助于胞内Ca 2+信号的空间调节。
Although spatially restricted Ca2+ release from the endoplasmic reticulum (ER) through intracellular Ca2+ channels plays important roles in various neuronal activities, the accurate distribution and dynamics of ER in the dendrite of living neurons still remain unknown. To elucidate these, we expressed fluorescent protein-tagged ER proteins in cultured mouse hippocampal neurons, and monitored their movements using time-lapse microscopy. We report here that a sub-compartment of ER forms in relatively large vesicles that are capable, similarly to the reticular ER, of taking up and releasing Ca2+. The vesicular sub-compartment of ER moved rapidly along the dendrites in both anterograde and retrograde directions at a velocity of 0.2-0.3 mum/second. Depletion of microtubules, overexpression of dominant-negative kinesin and kinesin depletion by antisense DNA reduced the number and velocity of the moving vesicles, suggesting that kinesin may drive the transport of the vesicular sub-compartment of ER along microtubules in the dendrite. Rapid transport of the Ca2+-releasable sub-compartment of ER might contribute to rapid supply of fresh ER proteins to the distal part of the dendrite, or to the spatial regulation of intracellular Ca2+ signaling.