MDR1 function is sensitive to the phosphorylation state of myosin regulatory light chain

Gaurav Bajaj, Rosita Rodriguez-Proteau, Anand Venkataraman, Ying Fan, Chrissa Kioussi, Jane E. Ishmael

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Multiple drug resistance protein 1 (MDR1) is composed of two homologous halves separated by an intracellular linker region. The linker has been reported to bind myosin regulatory light chain (RLC), but it is not clear how this can occur in the context of a myosin II complex. We characterized MDR1-RLC interactions and determined that binding occurs via the amino terminal of the RLC, a domain that typically binds myosin heavy chain. MDR1-RLC interactions were sensitive to the phosphorylation state of the light chain in that phosphorylation by myosin light chain kinase (MLCK) resulted in a loss of binding in vitro. We used ML-7, a specific inhibitor of MLCK, to study the functional consequences of disrupting RLC phosphorylation in intact cells. Pretreatment of polarized Madin-Darby canine kidney cells stably expressing MDR1 with ML-7 produced a significant increase in apical to basal permeability and a corresponding decrease in the efflux ratio (threefold; p<0.01) of [3H]-digoxin, a classic MDR1 substrate. Together these data show that MDR1-mediated transport of [3H]-digoxin can be modulated by pharmacological manipulation of myosin RLC, but direct MDR1-RLC interactions are atypical and not explained by the structure of the myosin II holoenzyme.

Original languageEnglish (US)
Pages (from-to)7-12
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Jul 2010
Externally publishedYes


  • Digoxin
  • Myosin light chain kinase
  • NMDA receptor
  • Nonmuscle myosin II
  • Regulatory light chain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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