SUN protection for the skin

LINC complexes, consisting of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins, connect the nucleus to the cytoskeleton, transmitting forces that control the nucleus's position within the cell. But how LINC complexes affect the cytoskeleton, and thus the balance of forces across cells and tissues, is less well understood. Stewart et al. now demonstrate that the LINC complex component SUN2 organizes the cyto-skeleton of epidermal keratinocytes, thereby controlling the localization and stability of the desmosomal adhesions that maintain epidermal integrity (1). LINC complexes interact with the actin, microtubule, and intermediate fi lament cyto-skeletons (2), as do various types of inter-cellular adhesions. Nuclei may therefore be physically linked to cell–cell contacts. In epithelial cells, for example, nuclei are drawn toward cadherin-based adherens junctions (3). Rachel Stewart, a Yale University graduate student co-mentored by Megan King, who studies the function of LINC complexes, and Valerie Horsley, an expert in mammalian skin development, found that nu-clei also move toward the adhesions formed between cultured keratinocytes (1). " We immediately thought that this had to involve the LINC complex, " King says. Stewart et al. therefore generated keratinocytes lacking the LINC complex protein SUN2, expecting that their nuclei would no longer move toward intercellular adhesions. " But instead we got the opposite result, " King continues. " The nuclei moved closer to the adhesions. " The researchers discovered that nuclei are pushed toward nascent cell–cell adhesions by actomyosin contractility. These forces are normally opposed by the microtubule cytoskeleton, but, in the absence of SUN2, keratinocyte microtubules were highly disorganized , allowing nuclei to be pushed closer than normal to intercellular contacts. Stewart and colleagues then turned their attention to how the loss of microtubule organization in SUN2-defi cient keratinocytes affected their intercellular adhesions. Micro-tubules are particularly important for the formation and maintenance of desmosomes, strong adhesions required to maintain the integrity of tissues, such as the skin, that are subject to mechanical stress (4, 5). " Desmo-somes form in keratinocytes lacking SUN2, " Horsley explains, " but they're in the wrong place and they're not mechanically stable. " In the absence of SUN2, des-mosomes were no longer distributed evenly around the sites of cell–cell contact and, when keratinocyte monolayers lacking SUN2 were subjected to mechanical stress, they fragmented much more easily than wild-type monolayers. The researchers then examined whether they could see similar effects on desmo-somes and epidermal integrity in vivo. …