ArticleBiophysical journal2025
Kinesin-1 autoinhibition tunes cargo transport by motor ensembles.
Article in Biophysical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Intracellular vesicular transport by kinesin-1 motors through numerous three-dimensional (3D) microtubule (MT) intersections must be regulated to support proper vesicle delivery. Knowing kinesin-1 can be regulated via autoinhibition, does kinesin-1 exhibit autoinhibition on cargo, and could this regulate vesicular transport through 3D MT intersections in vitro? To answer these questions, we compared liposome transport by ∼10 nearly full-length kinesin-1 motors with kinesin light chains bound (KinΔC) versus a constitutively active control (K543). In 3D MT intersections, KinΔC-liposomes terminate (48%) or go straight (43%) but rarely turn (9%), starkly contrasting K543-liposomes, which go straight (57%) or turn (31%) but rarely terminate (12%). On single MTs, KinΔC-liposomes have reduced run lengths and detachment forces versus K543-liposomes, suggesting autoinhibition reduces MT engagement, as supported by threefold lower KinΔC MT landing rates versus K543 and mechanistic in silico modeling. Furthermore, Kinesore, a small molecule that overcomes kinesin-1 autoinhibition, restores KinΔC's MT engagement. Thus, we propose that partial kinesin-1 autoinhibition while cargo bound may fine-tune cargo delivery to support physiological demands.
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