Yap Chan Choo, Winckler Bettina
Department of Cell Biology, University of Virginia, 1340 Jefferson Park Avenue, Pinn Hall 3226, Charlottesville, VA 22908, USA.
Autophagy Rep. 2022;1(1):570-575. doi: 10.1080/27694127.2022.2142888. Epub 2022 Nov 8.
Dendrites differ from axons in multiple ways, including the presence of minus-end out microtubules intermixed with the more conventional plus-end out microtubules. The mixed microtubule polarity makes regulation of directional transport in dendrites a challenge. Dynein can in principle be a retrograde and anterograde motor in dendrites. We show in our recent paper that dynein supports bi-directional transport of late endosomes in dendrites. We also show that overexpression of the RAB7 effector RILP which recruits dynein to late endosomes imparts retrograde bias onto late endosomes. Inhibition of dynein leads to a decrease in bi-directional motility of late endosomes, an expected result. Unexpectedly, inhibition of dynein also impairs endosome maturation as evidenced by increased association of GTP-RAB7 with late endosomes. Ultimately, dynein inhibition causes degradation defects of short-lived dendritic receptors and stunted dendrite morphologies. Much more work is required to fully understand how endosomal pathways are regulated in time and space in dendrites. Given the prevalence of neurological disorders where endosome-lysosome functions are impaired, this is a topic of great translational relevance.
树突在多个方面与轴突不同，包括存在与更常见的正端向外微管混合的负端向外微管。微管极性的混合使得树突中定向运输的调控成为一项挑战。动力蛋白原则上可以是树突中的逆行和顺行马达。我们在最近的论文中表明，动力蛋白支持树突中晚期内体的双向运输。我们还表明，将动力蛋白招募到晚期内体的RAB7效应器RILP的过表达赋予晚期内体逆行偏向。抑制动力蛋白会导致晚期内体双向运动性降低，这是预期的结果。出乎意料的是，抑制动力蛋白也会损害内体成熟，这表现为GTP-RAB7与晚期内体的关联增加。最终，动力蛋白抑制会导致短寿命树突受体的降解缺陷和树突形态发育不良。需要更多的工作来全面了解树突中内体途径在时间和空间上是如何被调控的。鉴于内体-溶酶体功能受损的神经疾病很普遍，这是一个具有重大转化意义的课题。
