Rac1-Mediated Endocytosis during Ephrin-A2- and Semaphorin 3A-Induced Growth Cone Collapse

Journal of Neuroscience - Tập 22 Số 14 - Trang 6019-6028 - 2002
William M. Jurney1, Gianluca Gallo2, Paul C. Letourneau2, Steven C. McLoon2
1Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA
2Department of Neuroscience, University of Minnesota, Minneapolis Minnesota 55455

Tóm tắt

Negative guidance molecules are important for guiding the growth of axons and ultimately for determining the wiring pattern in the developing nervous system. In tissue culture, growth cones at the tips of growing axons collapse in response to negative guidance molecules, such as ephrin-A2 and semaphorin 3A. The small GTPase Rac1 is involved in growth cone collapse, but the nature of its role is not clear. Rac1 activity assays showed that Rac1 is transiently inactivated after treatment with ephrin-A2. Ephrin-induced growth cone collapse, however, correlated with resumption of Rac1 activity. We demonstrate that Rac1 is required for endocytosis of the growth cone plasma membrane and reorganization of F-actin but not for the depolymerization of F-actin during growth cone collapse in response to ephrin-A2 and semaphorin 3A. Rac1, however, does not regulate constitutive endocytosis in growth cones. These findings show that in response to negative guidance molecules, the function of Rac1 changes from promoting actin polymerization associated with axon growth to driving endocytosis of the plasma membrane, resulting in growth cone collapse. Furthermore, Rac1 antisense injected into the embryonic chick eyein vivocaused the retinotectal projection to develop without normal topography in a manner consistent with Rac1 having an obligatory role in mediating ephrin signaling.

Từ khóa


Tài liệu tham khảo

10.1038/86011

Allen, 2000, A role for Drosophila Drac1 in neurite outgrowth and synaptogenesis in the giant fiber system., Mol Cell Neurosci, 6, 754, 10.1006/mcne.2000.0903

10.1016/S0896-6273(01)00556-6

10.1038/383525a0

10.1074/jbc.274.19.13198

10.1016/0092-8674(95)90426-3

10.1523/JNEUROSCI.19-21-09436.1999

Dorseuil, 1992, Inhibition of superoxide production in B lymphocytes by Rac antisense oligonucleotides., J Biol Chem, 267, 20540, 10.1016/S0021-9258(19)36716-X

10.1016/0092-8674(95)90425-5

10.1038/12963

10.1016/S0962-8924(99)01710-9

10.1523/JNEUROSCI.20-04-01458.2000

10.1016/0896-6273(95)90284-8

10.1016/S0896-6273(00)81060-0

10.1146/annurev.neuro.21.1.309

10.1083/jcb.149.2.411

10.1016/S0896-6273(00)80452-3

10.1126/science.279.5350.509

10.1523/JNEUROSCI.17-16-06256.1997

10.1002/1097-4695(200008)44:2<184::AID-NEU8>3.0.CO;2-N

10.1523/JNEUROSCI.19-06-01965.1999

10.1002/1097-4695(200008)44:2<126::AID-NEU4>3.0.CO;2-Z

Letourneau, 1996, The cytoskeleton in nerve growth cone motility and axonal pathfinding., Perspect Dev Neurobiol, 4, 111

10.1002/cm.970080302

10.1016/0092-8674(93)80064-L

10.1126/science.285.5429.895

10.1523/JNEUROSCI.09-04-01424.1989

10.1093/emboj/16.6.1258

10.1016/S0092-8674(00)80838-7

10.1016/S0092-8674(00)80565-6

10.1523/JNEUROSCI.19-19-08454.1999

10.1016/S0092-8674(00)81406-3

10.1016/S0896-6273(00)80368-2

10.1016/S0960-9822(99)80447-3

10.1083/jcb.149.2.263

10.1016/S0960-9822(00)00530-3

10.1523/JNEUROSCI.21-12-04318.2001

10.1006/dbio.1994.1321

10.1038/31735

Yates, 2001, Topographic-specific axon branching controlled by Ephrin-As is the critical event in retinotectal map development., J Neurosci, 21, 8548, 10.1523/JNEUROSCI.21-21-08548.2001

Thông tin
Thông tin xuất bản

Journal of Neuroscience

Tập 22 Số 14

6019-6028

Thông tin tác giả