The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport
The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport
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DOI：
10.1038/sj.emboj.7601609
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发表时间：
2007-03-21
期刊：
影响因子：
11.4
通讯作者：
Suzuki, Toshiharu
中科院分区：
文献类型：
--
作者：
Araki, Yoichi;Kawano, Takanori;Suzuki, Toshiharu
Alcadeinα(Alcα)是一种进化上保守的I型膜蛋白，在神经元中表达。我们发现AlCa通过一个新的含有色氨酸和天冬氨酸的序列与Kinesin轻链(K-D约为4-8×10(-9)M)发生强烈的结合。Alcα可诱导Kinesin-1与小泡结合，在轴突顺行转运中发挥新的作用。JNK相互作用蛋白1(JNK-Interaction Protein 1，JIP1)是一种激动素-1(kinesin-1，Kinesin-1)的适配蛋白，它干扰Alca的转运，使其与含Alcα的囊泡解离，并呈浓度依赖关系。含有Alcα的囊泡的运输速度与含有淀粉样β蛋白前体(APP)的囊泡的运输速度不同，后者由相同的Kinesin-1发动机运输。在活体轴突中，Alcα和APP囊泡主要由不同的群体组成。Alca与Kinesin-1的相互作用阻止了含有APP的囊泡的运输，并增加了β-淀粉样蛋白的生成。含有Alc和APP的囊泡与Kinesin-1的不适当相互作用可能会促进阿尔茨海默病患者APP的异常代谢。
Alcadein alpha (Alc alpha) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alca strongly associates with kinesin light chain (K-D approximate to 4-8 x 10(-9) M) through a novel tryptophan- and aspartic acid-containing sequence. Alc alpha can induce kinesin-1 association with vesicles and functions as a novel cargo in axonal anterograde transport. JNK-interacting protein 1 (JIP1), an adaptor protein for kinesin-1, perturbs the transport of Alca, and the kinesin-1 motor complex dissociates from Alc alpha-containing vesicles in a JIP1 concentration-dependent manner. Alc alpha-containing vesicles were transported with a velocity different from that of amyloid beta-protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor. Alc alpha- and APP-containing vesicles comprised mostly separate populations in axons in vivo. Interactions of Alca with kinesin-1 blocked transport of APP-containing vesicles and increased beta-amyloid generation. Inappropriate interactions of Alc- and APP-containing vesicles with kinesin-1 may promote aberrant APP metabolism in Alzheimer's disease.