Tuning Microtubule‐Based Transport Through Filamentous MAPs: The Problem of Dynein

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Abstract
We recently proposed that regulating the single‐to‐multiple motor transition was a likely strategy for regulating kinesin‐based transport in vivo. In this study, we use an in vitro bead assay coupled with an optical trap to investigate how this proposed regulatory mechanism affects dynein‐based transport. We show that tau’s regulation of kinesin function can proceed without interfering with dynein‐based transport. Surprisingly, at extremely high tau levels – where kinesin cannot bind microtubules (MTs) – dynein can still contact MTs. The difference between tau’s effects on kinesin‐ and dynein‐based motility suggests that tau can be used to tune relative amounts of plus‐end and minus‐end‐directed transport. As in the case of kinesin, we find that the 3RS isoform of tau is a more potent inhibitor of dynein binding to MTs. We show that this isoform‐specific effect is not because of steric interference of tau’s projection domains but rather because of tau’s interactions with the motor at the MT surface. Nonetheless, we do observe a modest steric interference effect of tau away from the MT and discuss the potential implications of this for molecular motor structure.