Ndel1 palmitoylation: A new mean to regulate cytoplasmic dynein activity

Anat Shmueli, Michal Segal, Tamar Sapir, Ryouhei Tsutsumi, Jun Noritake, Avi Bar, Sivan Sapoznik, Yuko Fukata, Irit Orr, Masaki Fukata, Orly Reiner

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Regulated activity of the retrograde molecular motor, cytoplasmic dynein, is crucial for multiple biological activities, and failure to regulate this activity can result in neuronal migration retardation or neuronal degeneration. The activity of dynein is controlled by the LIS1-Ndel1-Nde1 protein complex that participates in intracellular transport, mitosis, and neuronal migration. These biological processes are subject to tight multilevel modes of regulation. Palmitoylation is a reversible posttranslational lipid modification, which can dynamically regulate protein trafficking. We found that both Ndel1 and Nde1 undergo palmitoylation in vivo and in transfected cells by specific palmitoylation enzymes. Unpalmitoylated Ndel1 interacts better with dynein, whereas the interaction between Nde1 and cytoplasmic dynein is unaffected by palmitoylation. Furthermore, palmitoylated Ndel1 reduced cytoplasmic dynein activity as judged by Golgi distribution, VSVG and short microtubule trafficking, transport of endogenous Ndel1 and LIS1 from neurite tips to the cell body, retrograde trafficking of dynein puncta, and neuronal migration. Our findings indicate, to the best of our knowledge, for the first time that Ndel1 palmitoylation is a new mean for fine-tuning the activity of the retrograde motor cytoplasmic dynein.

Original languageEnglish
Pages (from-to)107-119
Number of pages13
JournalEMBO Journal
Volume29
Issue number1
DOIs
Publication statusPublished - 2010 Jan 6

Keywords

  • Dynein
  • Intracellular transport
  • Ndel1
  • Neuronal migration
  • Palmitoylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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