Competition Between Microtubule-Associated Proteins Directs Motor Transport

Nat Commun. 2018 Apr 16;9(1):1487. doi: 10.1038/s41467-018-03909-2.

Abstract

Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How the binding activities of non-motor MAPs are coordinated and how they contribute to the balance and distribution of motor transport is unknown. Here, we examine the relationship between MAP7 and tau owing to their antagonistic roles in vivo. We find that MAP7 and tau compete for binding to microtubules, and determine a mechanism by which MAP7 displaces tau from the lattice. MAP7 promotes kinesin-based transport in vivo and strongly recruits kinesin-1 to the microtubule in vitro, providing evidence for direct enhancement of motor motility by a MAP. Both MAP7 and tau strongly inhibit kinesin-3 and have no effect on cytoplasmic dynein, demonstrating that MAPs differentially control distinct classes of motors. Overall, these results reveal a general principle for how MAP competition dictates access to the microtubule to determine the correct distribution and balance of motor activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Transport
  • Drosophila melanogaster
  • Dyneins / genetics*
  • Dyneins / metabolism
  • Gene Expression
  • Humans
  • Kinesin / genetics*
  • Kinesin / metabolism
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Primary Cell Culture
  • Protein Binding
  • Swine
  • Tubulin / genetics*
  • Tubulin / metabolism
  • tau Proteins / genetics*
  • tau Proteins / metabolism

Substances

  • MAP7 protein, mouse
  • Mapt protein, mouse
  • Microtubule-Associated Proteins
  • Tubulin
  • epithelial microtubule-associate protein, 115 kDa
  • tau Proteins
  • Dyneins
  • Kinesin