TY - JOUR
T1 - Initial neurite outgrowth in drosophila neurons is driven by kinesin-powered microtubule sliding
AU - Lu, Wen
AU - Fox, Pangkong
AU - Lakonishok, Margot
AU - Davidson, Michael W.
AU - Gelfand, Vladimir I.
N1 - Funding Information:
We would like to acknowledge W. Saxton, M. Ross, C. Doe, I. Palacios, S. Rogers, the Bloomington Stock Center, and the Yale GFP Protein Trap Database for fly stocks and the Developmental Studies Hybridoma Bank for antibodies. Our special thanks are to Steffen Lemke for suggestions on RNA injections and to Gary Banker, Masha Gelfand, and Peter Hollenbeck for critical reading of the manuscript. We also would like to thank three reviewers for their insightful and valuable comments. Research reported here was supported by the National Institute of General Medical Science under award number R01GM052111.
PY - 2013/6/3
Y1 - 2013/6/3
N2 - Remarkably, forces within a neuron can extend its axon to a target that could be meters away. The two main cytoskeleton components in neurons are microtubules, which are mostly bundled along the axon shaft, and actin filaments, which are highly enriched in a structure at the axon distal tip, the growth cone. Neurite extension has been thought to be driven by a combination of two forces: pushing via microtubule assembly, and/or pulling by an actin-driven mechanism in the growth cone [1, 2]. Here we show that a novel mechanism, sliding of microtubules against each other by the microtubule motor kinesin-1, provides the mechanical forces necessary for initial neurite extension in Drosophila neurons. Neither actin filaments in the growth cone nor tubulin polymerization is required for initial outgrowth. Microtubule sliding in neurons is developmentally regulated and is suppressed during neuronal maturation. As kinesin-1 is highly evolutionarily conserved from Drosophila to humans, it is likely that kinesin-1-powered microtubule sliding plays an important role in neurite extension in many types of neurons across species.
AB - Remarkably, forces within a neuron can extend its axon to a target that could be meters away. The two main cytoskeleton components in neurons are microtubules, which are mostly bundled along the axon shaft, and actin filaments, which are highly enriched in a structure at the axon distal tip, the growth cone. Neurite extension has been thought to be driven by a combination of two forces: pushing via microtubule assembly, and/or pulling by an actin-driven mechanism in the growth cone [1, 2]. Here we show that a novel mechanism, sliding of microtubules against each other by the microtubule motor kinesin-1, provides the mechanical forces necessary for initial neurite extension in Drosophila neurons. Neither actin filaments in the growth cone nor tubulin polymerization is required for initial outgrowth. Microtubule sliding in neurons is developmentally regulated and is suppressed during neuronal maturation. As kinesin-1 is highly evolutionarily conserved from Drosophila to humans, it is likely that kinesin-1-powered microtubule sliding plays an important role in neurite extension in many types of neurons across species.
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U2 - 10.1016/j.cub.2013.04.050
DO - 10.1016/j.cub.2013.04.050
M3 - Article
C2 - 23707427
AN - SCOPUS:84878562310
SN - 0960-9822
VL - 23
SP - 1018
EP - 1023
JO - Current Biology
JF - Current Biology
IS - 11
ER -