Moved by Motors: Chromosome movement in interphase nuclei and the involvement of nuclear motor proteins.
We and others have documented rapid active movements of whole chromosomes and gene loci in interphase nuclei. This relocation of these chromosomal regions is to new non-random locations and can be multi-directional. We wanted to determine how these genomic regions were moved and why they moved. Using drugs and siRNA that inhibited the building of nuclear motors comprised of nuclear actin and myosin we were able to demonstrate that chromosomes and genes could no longer be moved both in human primary cells but also in the molluscan model organism Biomphalaria glabrata. This fresh-water snail is the obligate secondary host for the parasite Schistosoma mansoni that causes the dehabilitating disease Bilharzia/Schistosomiasis in tropical countries. The parasite causes specific gene relocation in the snail nuclei to facilitate its infection of this host.
Why there is a non-random relocation of the chromosomes and genes is not so clear – there are data for and against it being to regulate specific gene expression. However, in human cells that have reached replicative senescence and in old snails, chromosome/gene movement can no longer be induced and the nuclear motor proteins are not organised in the same way as they are in low passage number cells and young snails. Interestingly, in proliferating primary Hutchinson-Gilford Progeria Syndrome (HGPS) cells derived from patients with the classical lamin A mutation, the nuclear motors are distributed as they would be in non-proliferating cells and chromosome movement cannot be induced. Rapid chromosome movement and the correct distribution of nuclear motor proteins is only restored when the cells are treated with a farnesyltransferase inhibitor (FTI) drug.
Brunel University London, UK