Dual Regulation of Mammalian Myosin VI Motor Function

Misako Yoshimura, Kazuaki Homma, Junya Saito, Akira Inoue, Reiko Ikebe, Mitsuo Ikebe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Myosin VI is expressed in a variety of cell types and is thought to play a role in membrane trafficking and endocytosis, yet its motor function and regulation are not understood. The present study clarified mammalian myosin VI motor function and regulation at a molecular level. Myosin VI ATPase activity was highly activated by actin with Kactin of 9 μM. A predominant amount of myosin VI bound to actin in the presence of ATP unlike conventional myosins. KATP was much higher than those of other known myosins, suggesting that myosin VI has a weak affinity or slow binding for ATP. On the other hand, ADP markedly inhibited the actin-activated ATPase activity, suggesting a high affinity for ADP. These results suggested that myosin VI is predominantly in a strong actin binding state during the ATPase cycle. p21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr406. The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI. On the other hand, Ca 2+ diminished the actin-translocating activity of myosin VI although the actin-activated ATPase activity was not affected by Ca2+. Calmodulin was not dissociated from the heavy chain at high Ca2+, suggesting that a conformational change of calmodulin upon Ca2+ binding, but not its physical dissociation, determines the inhibition of the motility activity. The present results revealed the dual regulation of myosin VI by phosphorylation and Ca2+ binding to calmodulin light chain.

Original languageEnglish (US)
Pages (from-to)39600-39607
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number43
DOIs
StatePublished - Oct 26 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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