CD98hc (SLC3A2) is a key regulator of keratinocyte adhesion

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• 作者：Gilles Lemaî ; tre^a ; ^b ; ^{glemaitre@istem.fr} ; Alexandre Stella^c ; Jessica Feteira^a ; ^b ; Christine Baldeschi^a ; ^b ; Pierre Vaigot^a ; Michè ; le T. Martin^a ; Bernard Monsarrat^c ; Gilles Waksman^a ; ^b ; ¹
• 关键词：Keratinocytes ; Adhesion ; CD98hc ; Integrin ; Protein complexes ; LTQ-FT-Orbitrap
• 刊名：Journal of Dermatological Science
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：61
• 期：3
• 页码：169-179
• 全文大小：908 K

文摘

Background

Adhesion of keratinocytes is crucial for maintaining the integrity of the skin, as demonstrated by the number of dermatological disorders of genetic origin that are associated with a defect of basal keratinocyte adhesion. Integrins are the main component of the molecular networks involved in this phenomenon, but there are many others. In a recent description of proteins associated to caveolae at the plasma membrane of human basal epidermal cells, we demonstrated that CD98hc is localized with β1 integrin.

Objectives

We investigated the CD98hc proteins interactions and the role of CD98hc in keratinocyte adhesion.

Methods

CD98hc protein interaction was identified following co-immunoprecipitation and proteomic analysis using LTQ-FT mass spectrometer. Extinction of CD98hc gene expression using specific short hairpin RNA or over-expression of CD98hc lacking the β1 integrin binding site was used to evaluate the role of this protein in keratinocyte fate.

Results

We show that CD98hc forms molecular complexes with β1 and β4 integrins in primary human keratinocytes and, using immunofluorescence, that these complexes are localized at the plasma membrane, in keeping with a role in adhesion. We confirmed that this protein is a key player of keratinocyte adhesion because in absence of interaction between CD98hc and integrins, β1 integrin failed to translocate from the cytoplasm to the plasma membrane and keratinocytes expressed epidermal differentiation markers.

Conclusions

All these data strongly suggested that CD98hc is involved in integrin trafficking and by consequence, in keratinocyte adhesion and differentiation.