Steric inhibition of cytoplasmic dynein and kinesin motility by MAP2

Luis A. Lopez, Michael P. Sheetz

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Using several in vitro motility assays, we found that motility driven by the microtubule (MT) motors, kinesin and cytoplasmic dynein, could be inhibited by MAP2 but not by tau protein or the MT‐binding proteolytic fragment of MAP2. In MT gliding assays, even the presence of one MAP2 molecule per sixty‐nine tubulin dimers caused an inhibition of about 75% of MT motility at low concentrations of both motors. The percent inhibition of motility decreased with increasing concentration of either motor, suggesting that the inhibition was the result of competition for access to the MT surface. The decrease in the number of moving MTs with MAP2 was correlated with an increase in the frequency of release of moving MTs from the motor‐coated glass. In assays of in vitro vesicular organelle motility and formation of ER networks, the presence of MAP2 inhibited small vesicle movements and to a lesser extent ER network formation. To determine if competition for specific sites on the MT or coating of the MT surface inhibited motility, we used tau protein and the chymotryptic MT‐binding fragments of MAP2 to coat MTs. No inhibition was observed and there was even an increase in the number of attached and moving MTs in the gliding assay with tau‐coated MTs. Because MAP2, tau and the chymotryptic MT‐binding fragments of MAP2 bind to the same domain on tubulin, masking of the MT surface sites does not appear responsible for the inhibition of motility by MAP2. Rather, we suggest that the sidearm of MAP2 interfered with the interaction of motors with MTs and caused a dramatic increase in the rate of MT release. In vivo, MAP2 could play a major role in the generation of cellular polarity even at substoichiometric levels by inhibiting transport on microtubules in specific domains of the cytoplasm. © 1993 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalCell Motility and the Cytoskeleton
Issue number1
StatePublished - 1993
Externally publishedYes


  • MAPs
  • cytoplasmic dynein
  • kinesin
  • microtubules
  • motility

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology


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