TY - JOUR
T1 - Ndel1 palmitoylation
T2 - A new mean to regulate cytoplasmic dynein activity
AU - Shmueli, Anat
AU - Segal, Michal
AU - Sapir, Tamar
AU - Tsutsumi, Ryouhei
AU - Noritake, Jun
AU - Bar, Avi
AU - Sapoznik, Sivan
AU - Fukata, Yuko
AU - Orr, Irit
AU - Fukata, Masaki
AU - Reiner, Orly
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2010/1/6
Y1 - 2010/1/6
N2 - 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.
AB - 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.
KW - Dynein
KW - Intracellular transport
KW - Ndel1
KW - Neuronal migration
KW - Palmitoylation
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U2 - 10.1038/emboj.2009.325
DO - 10.1038/emboj.2009.325
M3 - Article
C2 - 19927128
AN - SCOPUS:75649100553
VL - 29
SP - 107
EP - 119
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 1
ER -