title: Cyclin D1 localizes in the cytoplasm of keratinocytes during skin differentiation and regulates cell-matrix adhesion.
abstract: The function of Cyclin D1 (CycD1) has been widely studied in the cell nucleus as a regulatory subunit of the cyclin-dependent kinases Cdk4/6 involved in the control of proliferation and development in mammals. CycD1 has been also localized in the cytoplasm, where its function nevertheless is poorly characterized. In this work we have observed that in normal skin as well as in primary cultures of human keratinocytes, cytoplasmic localization of CycD1 correlated with the degree of differentiation of the keratinocyte. In these conditions, CycD1 co-localized in cytoplasmic foci with exocyst components (Sec6) and regulators (RalA), and with β1 integrin, suggesting a role for CycD1 in the regulation of keratinocyte adhesion during differentiation. Consistent with this hypothesis, CycD1 overexpression increased β1 integrin recycling and drastically reduced the ability of keratinocytes to adhere to the extracellular matrix. We propose that localization of CycD1 in the cytoplasm during skin differentiation could be related to the changes in detachment ability of keratinocytes committed to differentiation.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques; Universitat de Lleida; Institut de Recerca Biomèdica de Lleida (IRBLleida); Lleida, Catalonia, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Fernández-Hernández
authors.forename: Marta
authors.initials: M
authors.lastname: Rafel
authors.forename: Noel P
authors.initials: NP
authors.lastname: Fusté
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Aguayo
authors.forename: Josep M
authors.initials: JM
authors.lastname: Casanova
authors.forename: Joaquim
authors.initials: J
authors.lastname: Egea
authors.forename: Francisco
authors.initials: F
authors.lastname: Ferrezuelo
authors.forename: Eloi
authors.initials: E
authors.lastname: Garí
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport; D012867:Skin / Q000166:cytology*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D019012:Integrin beta1; D033921:Vesicular Transport Proteins; D019938:Cyclin D1
keywords: cell adhesion; cyclin D1; cytoplasm; keratinocytes; β1 integrin