A dominant mutation inmec-7/β-tubulinaffects axon development and regeneration inCaenorhabditis elegansneurons

Molecular Biology of the Cell - Tập 24 Số 3 - Trang 285-296 - 2013
Leonie Kirszenblat1, Brent Neumann1, Sean Coakley1, Massimo A. Hilliard1
1Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia

Tóm tắt

Microtubules have been known for decades to be basic elements of the cytoskeleton. They form long, dynamic, rope-like structures within the cell that are essential for mitosis, maintenance of cell shape, and intracellular transport. More recently, in vitro studies have implicated microtubules as signaling molecules that, through changes in their stability, have the potential to trigger growth of axons and dendrites in developing neurons. In this study, we show that specific mutations in the Caenorhabditis elegans mec-7/β-tubulin gene cause ectopic axon formation in mechanosensory neurons in vivo. In mec-7 mutants, the ALM mechanosensory neuron forms a long ectopic neurite that extends posteriorly, a phenotype that can be mimicked in wild-type worms with a microtubule-stabilizing drug (paclitaxel), and suppressed by mutations in unc-33/CRMP2 and the kinesin-related gene, vab-8. Our results also reveal that these ectopic neurites contain RAB-3, a marker for presynaptic loci, suggesting that they have axon-like properties. Interestingly, in contrast with the excessive axonal growth observed during development, mec-7 mutants are inhibited in axonal regrowth and remodeling following axonal injury. Together our results suggest that MEC-7/β-tubulin integrity is necessary for the correct number of neurites a neuron generates in vivo and for the capacity of an axon to regenerate.

Từ khóa


Tài liệu tham khảo

Abe N, 2008, Curr Opin Neurobiol, 18, 276, 10.1016/j.conb.2008.06.005

Adler CE, 2006, Nat Neurosci, 9, 511, 10.1038/nn1666

Baas PW, 2002, Nat Cell Biol, 4, E194, 10.1038/ncb0802-e194

Baas PW, 2011, Dev Neurobiol, 71, 403, 10.1002/dneu.20818

Baran R, 2010, PLoS One, 5, e9655, 10.1371/journal.pone.0009655

Bounoutas A, 2009, Curr Biol, 19, 1362, 10.1016/j.cub.2009.06.036

Bradke F, 1999, Science, 283, 1931, 10.1126/science.283.5409.1931

Brenner S, 1974, Genetics, 77, 71, 10.1093/genetics/77.1.71

Chalfie M, 1981, Dev Biol, 82, 358, 10.1016/0012-1606(81)90459-0

Chalfie M, 1982, J Cell Biol, 93, 15, 10.1083/jcb.93.1.15

Chang C, 2006, Curr Biol, 16, 854, 10.1016/j.cub.2006.03.083

Chen L, 2011, Neuron, 71, 1043, 10.1016/j.neuron.2011.07.009

Davis MW, 2006, Methods Mol Biol, 351, 75

Davis MW, 2005, BMC Genomics, 6, 118, 10.1186/1471-2164-6-118

Erturk A, 2007, J Neurosci, 27, 9169, 10.1523/JNEUROSCI.0612-07.2007

Fojo T, 2008, The Role of Microtubules in Cell Biology, Neurobiology, and Oncology, 10.1007/978-1-59745-336-3

Fukata Y, 2002, Nat Cell Biol, 4, 583, 10.1038/ncb825

Ghosh-Roy A, 2011, J Neurosci, 30, 3175, 10.1523/JNEUROSCI.5464-09.2010

Goedert M, 1996, J Cell Sci, 109, 2661, 10.1242/jcs.109.11.2661

Hall DH, 1991, Cell, 65, 837, 10.1016/0092-8674(91)90391-B

Hamelin M, 1992, EMBO J, 11, 2885, 10.1002/j.1460-2075.1992.tb05357.x

Hedgecock EM, 1985, Dev Biol, 111, 158, 10.1016/0012-1606(85)90443-9

Hellal F, 2011, Science, 331, 928, 10.1126/science.1201148

Hilliard MA, 2006, Dev Cell, 10, 379, 10.1016/j.devcel.2006.01.013

Hoogenraad CC, 2009, Trends Cell Biol, 19, 669, 10.1016/j.tcb.2009.08.006

Howard J, 2003, Nature, 422, 753, 10.1038/nature01600

Inagaki N, 2001, Nat Neurosci, 4, 781, 10.1038/90476

Jacobson C, 2006, Neuron, 49, 797, 10.1016/j.neuron.2006.02.005

Jiang H, 2005, Cell, 120, 123

Kishi M, 2005, Science, 307, 929, 10.1126/science.1107403

Kuijpers M, 2011, Mol Cell Neurosci, 48, 349, 10.1016/j.mcn.2011.05.004

Kumar J, 2011, PLoS Genet, 6, e1001200, 10.1371/journal.pgen.1001200

Lai T, 2004, Development, 131, 5991, 10.1242/dev.01457

Levy-Strumpf N, 2007, Nat Neurosci, 10, 161, 10.1038/nn1835

10.1091/mbc.e05-12-1170

Maniar TA, 2012, Nat Neurosci, 15, 48, 10.1038/nn.2970

Namba T, 2011, Dev Neurobiol, 71, 445, 10.1002/dneu.20876

Neukirchen D, 2011, Semin Cell Dev Biol, 22, 825, 10.1016/j.semcdb.2011.08.007

Neumann B, 2011, Dev Dyn, 240, 1365, 10.1002/dvdy.22606

Nishimura T, 2004, Nat Cell Biol, 6, 328, 10.1038/ncb1118

Nonet ML, 1999, J Neurosci Methods, 89, 33, 10.1016/S0165-0270(99)00031-X

Nonet ML, 1997, J Neurosci, 17, 8061, 10.1523/JNEUROSCI.17-21-08061.1997

Ou CY, 2011, Cell, 141, 846

Pan CL, 2008, Dev Cell, 14, 132, 10.1016/j.devcel.2007.12.001

Polleux F, 2010, Cold Spring Harb Perspect Biol, 2, a001925, 10.1101/cshperspect.a001925

Prasad BC, 2006, Development, 133, 1757, 10.1242/dev.02357

Quinn CC, 2008, Curr Biol, 18, 808, 10.1016/j.cub.2008.04.050

Sambrook J, 2001, Molecular Cloning, 3

Sanchez-Alvarez L, 2011, PLoS Genet, 7, e1002257, 10.1371/journal.pgen.1002257

Savage C, 1989, Genes Dev, 3, 870, 10.1101/gad.3.6.870

Savage C, 1994, J Cell Sci, 107, 2165, 10.1242/jcs.107.8.2165

Sengottuvel V, 2011, Commun Integr Biol, 4, 391, 10.4161/cib.15552

Shi SH, 2004, Curr Biol, 14, 2025, 10.1016/j.cub.2004.11.009

Spencer AG, 2001, Proc Natl Acad Sci USA, 98, 13132, 10.1073/pnas.241504098

Steven R, 1998, Cell, 92, 785, 10.1016/S0092-8674(00)81406-3

Stiess M, 2011, Dev Neurobiol, 71, 430, 10.1002/dneu.20849

10.1091/mbc.e09-11-0967

Tischfield MA, 2011, Curr Opin Genet Dev, 21, 286, 10.1016/j.gde.2011.01.003

Tsuboi D, 2005, J Neurochem, 95, 1629, 10.1111/j.1471-4159.2005.03490.x

Watari-Goshima N, 2007, Nat Neurosci, 10, 169, 10.1038/nn1834

White JG, 1986, Philos Trans R Soc Lond B Biol Sci, 314, 1, 10.1098/rstb.1986.0056

Wicks SR, 2001, Nat Genet, 28, 160, 10.1038/88878

Wightman B, 1996, Development, 122, 671, 10.1242/dev.122.2.671

Witte H, 2008, Curr Opin Neurobiol, 18, 479, 10.1016/j.conb.2008.09.019

Witte H, 2008, J Cell Biol, 180, 619, 10.1083/jcb.200707042

Wolf FW, 1998, Neuron, 20, 655, 10.1016/S0896-6273(00)81006-5

Wu Z, 2007, Proc Natl Acad Sci USA, 104, 15132, 10.1073/pnas.0707001104

Yanik MF, 2006, IEEE J Sel Top Quant, 1283, 10.1109/JSTQE.2006.879579

Yoshimura T, 2005, Cell, 120, 137, 10.1016/j.cell.2004.11.012

Thông tin
Thông tin xuất bản

Molecular Biology of the Cell

Tập 24 Số 3

285-296

Thông tin tác giả