Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle

Mol Cell Biol. 2003 Feb;23(4):1239-50. doi: 10.1128/MCB.23.4.1239-1250.2003.


Emerging evidence supports the idea that a signaling pathway containing orthologs of at least mammalian NudE and Nudel, Lis1, and cytoplasmic dynein is conserved for eukaryotic nuclear migration. In mammals, this pathway has profound impact on neuronal migration during development of the central nervous system. Lis1 and dynein are also involved in other cellular functions, such as mitosis. Here we show that Nudel also participates in a subset of dynein function in M phase. Nudel was specifically phosphorylated in M phase in its serine/threonine phosphorylation motifs, probably by Cdc2 and also Erk1 and -2. A fraction of Nudel bound to centrosomes strongly in interphase and localized to mitotic spindles in early M phase. By using mutants incapable of or simulating phosphorylation, we confirmed that phosphorylation of Nudel regulated the cell-cycle-dependent distribution, possibly by increasing its dissociation rate at the microtubule-organizing center. Moreover, phosphorylated Nudel or the phosphorylation-mimicking mutant bound Lis1 more efficiently. We further demonstrated that a Nudel mutant incapable of binding to Lis1 impaired the poleward movement of dynein and hence the dynein-mediated transport of kinetochore proteins to spindle poles along microtubules, a process contributing to inactivation of the spindle checkpoint in mitosis. These results point to the importance of Nudel-Lis1 interaction for the dynein activity in M phase and to a possible role of Nudel phosphorylation as facilitating such interaction. In addition, comparative studies suggest that NudE is also functionally related to its paralog, Nudel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Adenosine Triphosphate / metabolism
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Centrosome / metabolism
  • Cytoplasm / metabolism
  • Dyneins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / immunology
  • Fungal Proteins / metabolism*
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitosis / physiology
  • Mutation
  • Phosphorylation
  • Protein Transport
  • Spindle Apparatus / metabolism*


  • Cell Cycle Proteins
  • Fungal Proteins
  • Microtubule-Associated Proteins
  • RO-11 protein, Neurospora crassa
  • Adenosine Triphosphate
  • CDC2 Protein Kinase
  • Mitogen-Activated Protein Kinase 1
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PAFAH1B1 protein, human
  • Dyneins