Up-regulation of loricrin expression by cell adhesion molecule nectin-1 through Rap1-ERK signaling in keratinocytes.
Nectin is an immunoglobulin-like cell-cell adhesion molecule, which plays essential roles in the initial step of formation of adherens junctions and tight junctions. We demonstrate here the role of nectin-1 in the epidermis using nectin-1-/- mice. Newborn nectin-1-/- pups showed shiny and slightly reddish skin; the amount of loricrin, one of the differentiation markers and also a major component of cornified cell envelopes, was markedly reduced in the epidermis of nectin-1-/- mice. The amounts of repetin and SPRRP, other components of cornified cell envelopes, were markedly elevated probably due to a compensatory mechanism to overcome the impaired expression of loricrin. However, cornified cells from nectin-1-/- mice were sensitive to mechanical stress. Moreover, Ca2+-induced activation of ERK through Rap1 and expression of loricrin were reduced in primary cultured nectin-1-/- keratinocytes; in turn, the inhibition of ERK activation reduced the amount of loricrin in wild-type keratinocytes. These results indicate that nectin-1 plays a key role in the expression of loricrin in the epidermis.
Wakamatsu
Kotaro
K
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Ogita
Hisakazu
H
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Okabe
Noriko
N
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Irie
Kenji
K
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Tanaka-Okamoto
Miki
M
Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
Ishizaki
Hiroyuki
H
Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
Ishida-Yamamoto
Akemi
A
Department of Dermatology, Asahikawa Medical College, Asahikawa, Hokkaido 078-8510, Japan.
Iizuka
Hajime
H
Department of Dermatology, Asahikawa Medical College, Asahikawa, Hokkaido 078-8510, Japan.
Miyoshi
Jun
J
Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
Takai
Yoshimi
Y
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan. Electronic address: ytakai@molbio.med.osaka-u.ac.jp.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D000075983:Nectins; D010766:Phosphorylation; D009418:S100 Proteins / Q000096:biosynthesis; D015854:Up-Regulation; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C000619015:Nectin1 protein, mouse; D000075983:Nectins; C108628:Rptn protein, mouse; D009418:S100 Proteins; C064554:loricrin; D048049:Extracellular Signal-Regulated MAP Kinases; D020827:rap1 GTP-Binding Proteins; D002118:Calcium