Analysis of neuronal kinesin-1 activation dynamics in response to cargo binding

驱动蛋白-1马达驱动极化的长距离运输沿着微管：在神经元轴突中的距离可以是几米，需要几天甚至几周。轴突运输的缺陷始终与神经退行性疾病（例如阿尔茨海默氏病、帕金森氏病、亨廷顿氏病、ALS）有关，并且了解分子细节对于提供新的干预途径至关重要。驱动蛋白在失活时被折叠和自动抑制，并且有效的运输需要展开和稳定的货物招募。虽然轴突货物可以以驱动蛋白的最大速度运输（快速轴突运输，FAT），但大多数新合成的蛋白质的移动速度要慢10至100倍（慢速轴突运输，SAT）。我们假设有货物的具体差异，在招聘和保留驱动蛋白在一个高度进行性的构象。

Kinesin-1 motors power polarised long-range transport along microtubules: distances covered by can be metres in neuronal axons, taking days or even weeks. Defects in axonal transport are consistently implicated in neurodegenerative disease (e.g. Alzheimer's, Parkinson's, Huntington's, ALS) and understanding the molecular details is crucial to providing new avenues for intervention. Kinesin is folded and auto-inhibited when inactive, and efficient transport requires both unfolding and stable recruitment to cargo. Although axonal cargoes can be transported at kinesin's maximum speed (Fast Axonal Transport, FAT), the majority of newly synthesised protein moves 10 to 100 times more slowly (Slow Axonal Transport, SAT). We hypothesise there are cargo specific differences in recruitment and retention of kinesin in a highly processive conformation.