Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions
- PMID: 25963820
- PMCID: PMC4427780
- DOI: 10.1083/jcb.201502024
Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions
Abstract
The linker of nucleoskeleton and cytoskeleton (LINC) complex allows cells to actively control nuclear position by coupling the nucleus to the cytoplasmic cytoskeleton. Nuclear position responds to the formation of intercellular adhesions through coordination with the cytoskeleton, but it is not known whether this response impacts adhesion function. In this paper, we demonstrate that the LINC complex component SUN2 contributes to the mechanical integrity of intercellular adhesions between mammalian epidermal keratinocytes. Mice deficient for Sun2 exhibited irregular hair follicle intercellular adhesions, defective follicle structure, and alopecia. Primary mouse keratinocytes lacking Sun2 displayed aberrant nuclear position in response to adhesion formation, altered desmosome distribution, and mechanically defective adhesions. This dysfunction appeared rooted in a failure of Sun2-null cells to reorganize their microtubule network to support coordinated intercellular adhesion. Together, these results suggest that cross talk between the nucleus, cytoskeleton, and intercellular adhesions is important for epidermal tissue integrity.
© 2015 Stewart et al.
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References
-
- Bazzi H., Getz A., Mahoney M.G., Ishida-Yamamoto A., Langbein L., Wahl J.K. III, and Christiano A.M.. 2006. Desmoglein 4 is expressed in highly differentiated keratinocytes and trichocytes in human epidermis and hair follicle. Differentiation. 74:129–140 10.1111/j.1432-0436.2006.00061.x - DOI - PubMed
-
- Bellion A., Baudoin J.P., Alvarez C., Bornens M., and Métin C.. 2005. Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the Golgi/centrosome associated with centrosome splitting and myosin contraction at the rear. J. Neurosci. 25:5691–5699 10.1523/JNEUROSCI.1030-05.2005 - DOI - PMC - PubMed
-
- Borghi N., Sorokina M., Shcherbakova O.G., Weis W.I., Pruitt B.L., Nelson W.J., and Dunn A.R.. 2012. E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch. Proc. Natl. Acad. Sci. USA. 109:12568–12573 10.1073/pnas.1204390109 - DOI - PMC - PubMed
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