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

Lead Research Organisation: University of Sheffield
Department Name: Neurosciences

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
2109768 Studentship BB/M011151/1 30/09/2018 28/12/2022 Evelyn Smith