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Mutations in the microtubule (MT)-binding protein doublecortin (DCX) or in the MT-based molecular motor dynein result in lissencephaly. However, a functional link between DCX and dynein has not been defined. Here, we demonstrate that DCX negatively regulates dyneinmediated retrograde transport in neurons from Dcx -/y or Dcx -/y ;Dclk1 -/mice by reducing dynein's association with MTs and disrupting the composition of the dynein motor complex. Previous work showed an increased binding of thedoi:10.7554/elife.82218.sa1 fatcat:b7enfcz4djedbaadkpf3mqbssa