MAP7 family proteins regulate kinesin-1 recruitment and activation

J Cell Biol. 2019 Apr 1;218(4):1298-1318. doi: 10.1083/jcb.201808065. Epub 2019 Feb 15.

Abstract

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly to enable kinesin-1-dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared with MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be cotransported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • COS Cells
  • Chlorocebus aethiops
  • Diketopiperazines / pharmacology
  • Enzyme Activation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / drug effects
  • Microtubules / enzymology*
  • Microtubules / genetics
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Transport

Substances

  • Benzamides
  • Diketopiperazines
  • K560 compound
  • KIF5B protein, human
  • MAP7 protein, human
  • MAP7D1 protein, human
  • MAP7D3 protein, human
  • Microtubule-Associated Proteins
  • Kinesin