Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein activity.
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.
Shmueli
Anat
A
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Segal
Michal
M
Sapir
Tamar
T
Tsutsumi
Ryouhei
R
Noritake
Jun
J
Bar
Avi
A
Sapoznik
Sivan
S
Fukata
Yuko
Y
Orr
Irit
I
Fukata
Masaki
M
Reiner
Orly
O
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D054878:Lipoylation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C421108:NDEL1 protein, human; C525094:Nde1 protein, human; C531336:Nde1 protein, mouse; C486015:Ndel1 protein, mouse; D011994:Recombinant Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C513190:Pafah1b1 protein, mouse; D004398:Dyneins