Tuning microtubule-based transport through filamentous MAPs: the problem of dynein

Traffic. 2008 Jun;9(6):882-92. doi: 10.1111/j.1600-0854.2008.00741.x. Epub 2008 Mar 28.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport
  • Buffers
  • Dyneins / chemistry
  • Dyneins / physiology*
  • Kinesins / physiology
  • Microspheres
  • Microtubule-Associated Proteins / physiology*
  • Microtubules / physiology*
  • Polystyrenes / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Staphylococcal Protein A / metabolism
  • Tubulin / isolation & purification
  • tau Proteins / isolation & purification
  • tau Proteins / physiology

Substances

  • Buffers
  • Microtubule-Associated Proteins
  • Polystyrenes
  • Staphylococcal Protein A
  • Tubulin
  • tau Proteins
  • Dyneins
  • Kinesins