A model for non‐viral gene delivery: through syndecan adhesion molecules and powered by actin

Journal of Gene Medicine - Tập 6 Số 7 - Trang 769-776 - 2004
Idit Kopatz1, Jean-Serge Rémy1, Jean‐Paul Behr1
1Laboratoire de Chimie Génétique associé C.N.R.S./Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, BP 24, 67401 Illkirch, France

Tóm tắt

AbstractBackgroundCell transfection requires cationic DNA complexes and heparan sulfate proteoglycans (HSPGs) at the cell surface. Syndecans are transmembrane HSPGs that are ubiquitously expressed on adherent cells. Their polyanionic heparan sulfate moieties are bound at the distal end of their ectodomain, thus facilitating interaction with large cationic particles.MethodsWe propose a model for cell entry involving syndecans as receptors for the DNA complexes by comparing transfection with bacteria uptake and using drug inhibition experiments along with confocal microscopy.ResultsWhen combined with results from the literature, our data suggest the following sequence of events: after initial particle binding, gradual electrostatic zippering of the plasma membrane onto the particle is sustained by lateral diffusion of syndecan molecules that cluster into cholesterol‐rich rafts. Clustering in turn triggers PKC activity and linker protein‐mediated actin binding to the cytoplasmic tail of the syndecans. Resulting tension fibers and a growing network of cortical actin may then pull the particle into the cell.ConclusionsDiversion of integrin‐ and syndecan‐mediated cell adhesion processes for particle engulfment appears to be widely exploited by animals (chylomicrons), by pathogens (bacteria, viruses) and, as suggested here, by non‐viral vectors. Copyright © 2004 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1016/S0169-409X(01)00213-7

Labat‐Moleur F, 1996, Gene Ther, 3, 1010

10.1074/jbc.270.32.18997

10.1073/pnas.86.18.6982

10.1073/pnas.93.22.12349

10.1074/jbc.273.40.26164

10.1074/jbc.M011553200

10.1007/BF02456129

10.1083/jcb.116.5.1273

10.1128/JVI.72.2.1438-1445.1998

10.1006/viro.2001.1122

10.1083/jcb.123.3.759

10.1002/j.1460-2075.1995.tb07208.x

10.1126/science.276.5313.718

10.1006/excr.1998.4116

10.1046/j.1462-5822.2000.00036.x

10.1016/S0014-5793(98)00144-6

Grassme HU, 1996, Infect Immunol, 64, 1621, 10.1128/iai.64.5.1621-1630.1996

Boussif O, 1996, Gene Ther, 3, 1074

10.1016/S0074-7696(01)07004-8

10.1042/BJ20021228

Carey DJ, 1996, Perspect Dev Neurobiol, 3, 331

10.1006/excr.2000.4802

10.1016/S0962-8924(00)88962-X

10.1016/S0092-8674(00)81179-4

10.1242/jcs.101.2.277

10.1083/jcb.124.1.161

10.1006/excr.1994.1228

10.1091/mbc.7.11.1771

10.1083/jcb.103.6.2683

10.1089/10430349950016645

10.1016/S0022-2275(20)33334-4

10.1021/bi002417n

10.1073/pnas.94.26.14547

10.1172/JCI119685

Fuki IV, 2000, Biochem J, 351, 607, 10.1042/bj3510607

10.1091/mbc.5.7.797

10.1021/bc00030a021

10.1016/S0005-2736(00)00230-3

10.1074/jbc.274.19.13534

10.1073/pnas.0636277100

Thông tin
Thông tin xuất bản

Journal of Gene Medicine

Tập 6 Số 7

769-776

Thông tin tác giả