Disturbed nuclear orientation and cellular migration in A-type lamin deficient cells.
The nuclear lamina and the cytoskeleton form an integrated structure that warrants proper mechanical functioning of cells. We have studied the correlation between structural alterations and migrational behaviour in fibroblasts with and without A-type lamins. We show that loss of A-type lamins causes loss of emerin and nesprin-3 from the nuclear envelope, concurring with a disturbance in the connection between the nucleus and the cytoskeleton in A-type lamin-deficient (lmna -/-) cells. In these cells functional migration assays during in vitro wound healing revealed a delayed reorientation of the nucleus and the microtubule-organizing center during migration, as well as a loss of nuclear oscillatory rotation. These observations in fibroblasts isolated from lmna knockout mice were confirmed in a 3T3 cell line with stable reduction of lmna expression due to RNAi approach. Our results indicate that A-type lamins play a key role in maintaining directional movement governed by the cytoskeleton, and that the loss of these karyoskeletal proteins has important consequences for functioning of the cell as a mechanical entity.
Houben
F
F
Department of Molecular Cell Biology (Box 17), School for Cardiovascular Diseases (CARIM), Maastricht University, P.O. Box 616, NL-6200 MD Maastricht, The Netherlands. frederik.houben@molcelb.unimaas.nl
Willems
C H M P
CH
Declercq
I L J
IL
Hochstenbach
K
K
Kamps
M A
MA
Snoeckx
L H E H
LH
Ramaekers
F C S
FC
Broers
J L V
JL
D016475:3T3 Cells; D000818:Animals; D001681:Biological Assay; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D016764:Cell Polarity; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D034904:Lamin Type A / Q000172:deficiency* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D014945:Wound Healing
D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; C507800:nesprin-3 protein, mouse