期刊
JOURNAL OF CELL BIOLOGY
卷 185, 期 7, 页码 1243-1258出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200809044
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- NCI NIH HHS [T32 CA009151, R01 CA122151, CA122151, P30 CA060553-159026] Funding Source: Medline
- NIAMS NIH HHS [AR43380, R01 AR041836, R37 AR043380, R01 AR043380] Funding Source: Medline
- NIEHS NIH HHS [F30 ES14990, F30 ES014990] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008061, T32 GM08061] Funding Source: Medline
Dsg1 (desmoglein 1) is a member of the cadherin family of Ca2+-dependent cell adhesion molecules that is first expressed in the epidermis as keratinocytes transit out of the basal layer and becomes concentrated in the uppermost cell layers of this stratified epithelium. In this study, we show that Dsg1 is not only required for maintaining epidermal tissue integrity in the superficial layers but also supports keratinocyte differentiation and suprabasal morphogenesis. Dsg1 lacking N-terminal ectodomain residues required for adhesion remained capable of promoting keratinocyte differentiation. Moreover, this capability did not depend on cytodomain interactions with the armadillo protein plakoglobin or coexpression of its companion suprabasal cadherin, Dsc1 ( desmocollin 1). Instead, Dsg1 was required for suppression of epidermal growth factor receptor-Erk1/2 (extracellular signal-regulated kinase 1/2) signaling, thereby facilitating keratinocyte progression through a terminal differentiation program. In addition to serving as a rigid anchor between adjacent cells, this study implicates desmosomal cadherins as key components of a signaling axis governing epithelial morphogenesis.
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