Nuclear position is actively controlledand can be adjusted accordingto the needs of a cell by nuclear movement.Microtubules mediate the majorityof nuclear movements studied to date,although examples of nuclear movementsmediated by the actin cytoskeleton havebeen described. One such actin-dependentnuclear movement occurs during centrosomeorientation in fibroblasts polarizingfor migration. Here, the centrosome ismaintained at the cell center while thenucleus is moved to the cell rear by actinretrograde flow thus positioning the centrosomebetween the nucleus and theleading edge of the cell. We have exploredthe molecular mechanism for actin dependentmovement of the nucleus duringcentrosome orientation. We found thata novel linear array of nuclear envelopemembrane proteins composed of nesprin-2G and SUN2, called transmembraneactin-associated nuclear (TAN) lines,couple the nucleus to moving actin cablesresulting in the nucleus being positionedat the cell rear. TAN lines are anchored byA-type lamins and this allows the forcesgenerated by the actin cytoskeleton to betransmitted across the nuclear envelope tomove the nucleus. Here we review the datasupporting this mechanism for nuclearmovement, discuss questions remainingto be addressed and consider how this newmechanism of nuclear movement mayshed light on human disease.
Bibliographical noteFunding Information:
This work was supported by a Dystonia Medical Research Foundation Fellowship (G.W.G.L.), a Muscular Dystrophy Association grant (E.R.G.), an Association pour la Recherche sur le Cancer grant (E.R.G.), a Ligue Nacionale contre le Cancer grant (E.R.G.), an American Heart Association Fellowship (E.S.F.), a Dystonia Medical Research Foundation grant (G.G.G.) and NIH grants (GM06929) (G.G.G.) and NS059352 (H.J.W.).
- LINC complex
- TAN lines