title: Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation.
abstract: The skin water barrier, essential for terrestrial life, is formed by a multilayered stratifying epithelium, which shows a polarized distribution of both differentiation and intercellular junction markers. Recently, several reports showed the crucial importance of tight junctions for the in vivo water barrier function of the skin. In simple epithelial cells, intercellular junction formation is closely coupled to the establishment of polarity. However, if and how polarity proteins contribute to epidermal differentiation and junction formation is not yet known. Here, we have characterized the localization and isoform expression of the polarity protein atypical PKC (aPKC) and its binding partners Par3 and Par6 in epidermis and primary keratinocytes of mice. Their distribution is only partially overlapping in the granular layer, the site of functional tight junctions, suggesting that next to a common Par3/Par6/aPKC function they also may have functions independent of each other. Both aPKCzeta and aPKCiota/lambda, are expressed in the epidermis but only aPKCiota/lambda showed a strong enrichment in the junctions, suggesting that this aPKC isoform is important for epidermal tight junction function. Indeed, inhibition of aPKC function showed that endogenous aPKC is crucial for in vitro barrier function and this required the presence of both the Par3 and Par6 binding sites.
authors.affiliation: Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.forename: Annika
authors.initials: A
authors.lastname: Schmitz
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.forename: Christian
authors.initials: C
authors.lastname: Michels
authors.forename: Ingo
authors.initials: I
authors.lastname: Haase
authors.forename: André
authors.initials: A
authors.lastname: le Bivic
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Carien M
authors.initials: CM
authors.lastname: Niessen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D012867:Skin / Q000201:enzymology; D019108:Tight Junctions / Q000502:physiology*; D014018:Tissue Distribution; D014945:Wound Healing / Q000502:physiology; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta; C518597:Par6 protein, mouse; C115084:Pard3 protein, mouse