Myosin Va and Endoplasmic Reticulum Calcium Channel Complex Regulates Membrane Export during Axon Guidance
Myosin Va and Endoplasmic Reticulum Calcium Channel Complex Regulates Membrane Export during Axon Guidance
复制标题
肌球蛋白 Va 和内质网钙通道复合物在轴突引导过程中调节膜输出
DOI：
10.1016/j.celrep.2016.04.021
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发表时间：
2016
期刊：
影响因子：
8.8
通讯作者：
Kamiguchi H
中科院分区：
文献类型：
--
作者：
Wada F;Nakata A;Tatsu Y;Ooashi N;Fukuda T;Nabetani T;Kamiguchi H
在轴突引导过程中，生长锥通过在提示侧插入新膜来导航至有吸引力的提示。该过程依赖于内质网 (ER) Ca2+ 通道的 Ca2+ 释放，但控制这种不对称囊泡输出的 Ca2+ 传感器和效应器仍然未知。我们鉴定了一种控制不对称 ER Ca2+ 依赖性膜囊泡输出的蛋白质复合物。 Ca2+ 依赖性运动蛋白肌球蛋白 Va (MyoVa) 通过两个主要 ER Ca2+ 通道（肌醇 1,4,5-三磷酸和兰尼碱受体）上的共同结合位点将膜囊泡束缚到 ER。为了响应有吸引力的线索，来自 ER 通道的微摩尔 Ca2+ 会触发 MyoVa 通道解离以及释放的囊泡向线索侧移动，从而实现生长锥的转动。 MyoVa-Ca2+ 通道相互作用是体内脊髓发育过程中长程轴突正常生长所必需的。这些发现揭示了轴突引导中 Ca2+ 依赖性吸引力的内质网周围膜输出途径。
During axon guidance, growth cones navigate toward attractive cues by inserting new membrane on the cue side. This process depends on Ca2+release from endoplasmic reticulum (ER) Ca2+channels, but the Ca2+sensor and effector governing this asymmetric vesicle export remain unknown. We identified a protein complex that controls asymmetric ER Ca2+-dependent membrane vesicle export. The Ca2+-dependent motor protein myosin Va (MyoVa) tethers membrane vesicles to the ER via a common binding site on the two major ER Ca2+channels, inositol 1,4,5-trisphosphate and ryanodine receptors. In response to attractive cues, micromolar Ca2+from ER channels triggers MyoVa-channel dissociation and the movement of freed vesicles to the cue side, enabling growth cone turning. MyoVa-Ca2+channel interactions are required for proper long-range axon growth in developing spinal cord in vivo. These findings reveal a peri-ER membrane export pathway for Ca2+-dependent attraction in axon guidance.