Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes.
Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes.
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DOI：
10.7554/elife.74538
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发表时间：
2021-12-09
期刊：
影响因子：
7.7
通讯作者：
Reck-Peterson SL
中科院分区：
文献类型：
--
作者：
Christensen JR;Kendrick AA;Truong JB;Aguilar-Maldonado A;Adani V;Dzieciatkowska M;Reck-Peterson SL
在真核细胞中，细胞内组分由微管马达细胞质动力蛋白-1（动力蛋白）和驱动蛋白组织，其通过衔接蛋白连接到货物。当~40个驱动蛋白将货物运输到微管的正端时，单个动力蛋白将货物向相反方向移动。动力蛋白如何运输各种各样的货物仍然是一个悬而未决的问题。FTS-Hook-FHIP（“FHF”）货物衔接子复合物将动力蛋白与人类和真菌中的货物连接。由于人类细胞具有三种Hooks和四种FHIP蛋白，我们假设不同Hook和FHIP蛋白的组合组装可能是动力蛋白货物多样性的基础。使用蛋白质组学方法，我们确定每个FHIP蛋白的蛋白质“相互作用组”。活细胞成像和生物化学方法表明，不同的FHF复合物与不同的能动货物。这些复合物还与动力蛋白及其辅因子动力蛋白在单分子体外重建测定中一起移动。由FTS、FHIP 1B和Hook 1/Hook 3组成的复合物通过FHIP 1B和GTP结合的Rab 5之间的直接相互作用与Rab 5标记的早期内体共定位。相反，由FTS、FHIP 2A和Hook 2组成的复合物与Rab 1A标记的ER至高尔基体货物共定位，并且FHIP 2A参与Rab 1A小管的运动。我们的研究结果表明，不同的FTS-Hook-FHIP复合物的组合组装是动力蛋白用于实现货物特异性的一种机制。
In eukaryotic cells, intracellular components are organized by the microtubule motors cytoplasmic dynein-1 (dynein) and kinesins, which are linked to cargos via adaptor proteins. While ~40 kinesins transport cargo toward the plus end of microtubules, a single dynein moves cargo in the opposite direction. How dynein transports a wide variety of cargos remains an open question. The FTS–Hook–FHIP (‘FHF’) cargo adaptor complex links dynein to cargo in humans and fungi. As human cells have three Hooks and four FHIP proteins, we hypothesized that the combinatorial assembly of different Hook and FHIP proteins could underlie dynein cargo diversity. Using proteomic approaches, we determine the protein ‘interactome’ of each FHIP protein. Live-cell imaging and biochemical approaches show that different FHF complexes associate with distinct motile cargos. These complexes also move with dynein and its cofactor dynactin in single-molecule in vitro reconstitution assays. Complexes composed of FTS, FHIP1B, and Hook1/Hook3 colocalize with Rab5-tagged early endosomes via a direct interaction between FHIP1B and GTP-bound Rab5. In contrast, complexes composed of FTS, FHIP2A, and Hook2 colocalize with Rab1A-tagged ER-to-Golgi cargos and FHIP2A is involved in the motility of Rab1A tubules. Our findings suggest that combinatorial assembly of different FTS–Hook–FHIP complexes is one mechanism dynein uses to achieve cargo specificity.
DOI：
10.1083/jcb.119.5.1077
发表时间：
1992-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Schwaninger R;Plutner H;Bokoch GM;Balch WE
通讯作者：
Balch WE