Acetylated Microtubules Are Preferentially Bundled Leading to Enhanced Kinesin-1 Motility

Abstract

The motor proteins kinesin and dynein transport organelles, mRNA, proteins, and signaling molecules along the microtubule cytoskeleton. In addition to serving as tracks for transport, the microtubule cytoskeleton directs intracellular trafficking by regulating the activity of motor proteins through the organization of the filament network, microtubule-associated proteins, and tubulin posttranslational modifications. However, it is not well understood how these factors influence motor motility, and in vitro assays and live cell observations often produce disparate results. To systematically examine the factors that contribute to cytoskeleton-based regulation of motor protein motility, we extracted intact microtubule networks from cells and tracked the motility of single fluorescently labeled motor proteins on these cytoskeletons. We find that tubulin acetylation alone does not directly affect kinesin-1 motility. However, acetylated microtubules are predominantly bundled, and bundling enhances kinesin run lengths and provides a greater number of available kinesin binding sites. The neuronal MAP tau is also not sensitive to tubulin acetylation, but enriches preferentially on highly curved regions of microtubules where it strongly inhibits kinesin motility. Taken together, these results suggest that the organization of the microtubule network is a key contributor to the regulation of motor-based transport.

Microtubule Dysfunction: A Common Feature of Neurodegenerative Diseases

“…Biochemical experiments have shown that kinesin-1 selectively binds acetylated MTs; however, considering the lumen localization of K40, how this PTM influences kinesin binding is still unclear. It has been recently proposed that acetylated MTs, being enriched in high curve regions, can expose a greater number of available kinesin-binding sites and enhance kinesin run lengths [ 133 ].…”

Expression profiling of kinesins, involved in the development of autophagy in Arabidopsis thaliana, and the role of tubulin acetylation in the interaction of Atg8 protein with microtubules

“…Ранее было продемонстрировано, что ацетилирование тубулина само по себе не влияет на скорость и длину пробега кинезина-1 вдоль МТ в системе in vitro [15], однако ацетилированные МТ предпочтительнее собираются в пучки, приводя к усилению подвижности этого транспортного белка [16]. Поэтому нам казалось логичным также проверить потенциальное влияние ацетилирования на взаимодействие α-тубулина с белком Atg8.…”

The walkoff effect: cargo distribution implies motor type in bidirectional microtubule bundles

“…Depending on the cell type, MT networks are either unipolar, with all the MTs oriented in the same direction as in the vertebrate axons, or have mixed directionality as in vertebrate dendrites or epithelial cells [36][37][38][39][40][41]. Additionally, MTs form bundles, where several MTs are closely apposed, often connected by specialized cross-linking proteins [42][43][44], and unidirectional bundles facilitate intracellular transport [45,46]. On unidirectional networks, the overall outcome of transport is intuitive: towards the minus-or plus-ends depending on the motor type, however, this outcome is non-trivial in the case of MT networks with mixed directionality.…”