Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities.
Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities.
复制标题
DOI：
10.1016/j.jbc.2023.105084
复制
发表时间：
2023-09
影响因子：
4.8
通讯作者：
Cruz, Enrique De La
中科院分区：
文献类型：
--
作者：
Suber, Yani;Alam, Md Noor A.;Nakos, Konstantinos;Bhakt, Priyanka;Spiliotis, Elias T.;Cruz, Enrique De La
远程膜传输由微管相关蛋白和翻译后修饰引导，它们共同构成传输代码。这个编码的调控原则以及它如何协调运动蛋白和动力蛋白马达的运动在很大程度上是未知的。septin是gtp结合蛋白的一个大家族，它们组装成与微管相关的复合物。通过单分子体外运动测定，我们测试了微管相关的SEPT2/6/7、SEPT2/6/7/9和SEPT5/7/11复合物如何影响组成活性运动蛋白KIF5C和KIF1A以及动力蛋白-动力蛋白-双侧D （DDB）运动复合物的运动。我们发现微管相关的SEPT2/6/7是DDB和KIF5C的有效抑制剂，主要阻止它们与微管的关联。SEPT2/6/7也通过阻断微管的步进抑制KIF1A。在sept2 /6/7/9包被的微管上，KIF1A的抑制作用被SEPT9抑制，而SEPT9单独增强KIF1A，这表明单个septin亚基决定了septin复合物的调控特性。引人注目的是，SEPT5/7/11与SEPT2/6/7不同，允许KIF1A的运动性并将DDB固定在微管晶格上。在海马神经元中，丝状SEPT5与高尔基膜下的体树突微管共定位，缺乏SEPT6。SEPT5的缺失破坏了高尔基体形态和高尔基带向体近端树突轴的极化，这与SEPT5/7/11将DDB系在微管上的行为一致。总之，这些结果表明，微管相关复合物在调节微管马达的运动和定位方面具有不同的特异性。我们假设septin是基于微管的编码的一个组成部分，该编码在空间上控制膜交通。
Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory principles of this code and how it orchestrates the motility of kinesin and dynein motors are largely unknown. Septins are a large family of GTP-binding proteins, which assemble into complexes that associate with microtubules. Using single-molecule in vitro motility assays, we tested how the microtubule-associated SEPT2/6/7, SEPT2/6/7/9, and SEPT5/7/11 complexes affect the motilities of the constitutively active kinesins KIF5C and KIF1A and the dynein-dynactin-bicaudal D (DDB) motor complex. We found that microtubule-associated SEPT2/6/7 is a potent inhibitor of DDB and KIF5C, preventing mainly their association with microtubules. SEPT2/6/7 also inhibits KIF1A by obstructing stepping along microtubules. On SEPT2/6/7/9-coated microtubules, KIF1A inhibition is dampened by SEPT9, which alone enhances KIF1A, showing that individual septin subunits determine the regulatory properties of septin complexes. Strikingly, SEPT5/7/11 differs from SEPT2/6/7, in permitting the motility of KIF1A and immobilizing DDB to the microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes with somatodendritic microtubules that underlie Golgi membranes and lack SEPT6. Depletion of SEPT5 disrupts Golgi morphology and polarization of Golgi ribbons into the shaft of somato-proximal dendrites, which is consistent with the tethering of DDB to microtubules by SEPT5/7/11. Collectively, these results suggest that microtubule-associated complexes have differential specificities in the regulation of the motility and positioning of microtubule motors. We posit that septins are an integral part of the microtubule-based code that spatially controls membrane traffic.
登录
查看更多内容
影响因子：
5.5
作者：
Cavini IA;Leonardo DA;Rosa HVD;Castro DKSV;D'Muniz Pereira H;Valadares NF;Araujo APU;Garratt RC
通讯作者：
Garratt RC
影响因子：
16.2
作者：
Horton, AC;Rácz, B;Ehlers, MD
通讯作者：
Ehlers, MD
影响因子：
7.8
作者：
Garcia, Galo, III;Bertin, Aurelie;Nogales, Eva
通讯作者：
Nogales, Eva
神经元膜交通的极性需要在微管相关的SEPTIN进入树突期间对运动蛋白运动货物进行排序。
影响因子：
11.8
作者：
Karasmanis EP;Phan CT;Angelis D;Kesisova IA;Hoogenraad CC;McKenney RJ;Spiliotis ET
通讯作者：
Spiliotis ET
基于质谱的方法用于绘制蛋白质亚细胞定位，揭示了小鼠原代神经元的空间蛋白质组。
影响因子：
8.8
作者：
Itzhak DN;Davies C;Tyanova S;Mishra A;Williamson J;Antrobus R;Cox J;Weekes MP;Borner GHH
通讯作者：
Borner GHH