Email updates

Keep up to date with the latest news and content from BMC Dermatology and BioMed Central.

Open Access Research article

Functional expression of NF1 tumor suppressor protein: association with keratin intermediate filaments during the early development of human epidermis

Maria Malminen12, Sirkku Peltonen12*, Jussi Koivunen3 and Juha Peltonen134

Author Affiliations

1 Department of Medical Biochemistry, University of Turku, Turku, Finland

2 Department of Dermatology, University of Turku, Turku, Finland

3 Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

4 Department of Dermatology, University of Oulu, Oulu, Finland

For all author emails, please log on.

BMC Dermatology 2002, 2:10  doi:10.1186/1471-5945-2-10

Published: 29 August 2002

Abstract

Background

NF1 refers to type 1 neurofibromatosis syndrome, which has been linked with mutations of the large NF1 gene. NF1 tumor suppressor protein, neurofibromin, has been shown to regulate ras: the NF1 protein contains a GTPase activating protein (GAP) related domain which functions as p21rasGAP. Our studies have previously demonstrated that the NF1 protein forms a high affinity association with cytokeratin 14 during the formation of desmosomes and hemidesmosomes in cultured keratinocytes.

Methods

The expression of NF1 protein was studied in developing human epidermis using western transfer analysis, indirect immunofluorescence, confocal laser scanning microscopy, immunoelectron microscopy, and in situ hybridization.

Results

The expression of NF1 protein was noted to be highly elevated in the periderm at 8 weeks estimated gestational age (EGA) and in the basal cells at 8–14 weeks EGA. During this period, NF1 protein was associated with cytokeratin filaments terminating to desmosomes and hemidesmosomes. NF1 protein did not display colocalization with α-tubulin or actin of the cytoskeleton, or with adherens junction proteins.

Conclusions

These results depict an early fetal period when the NF1 tumor suppressor is abundantly expressed in epidermis and associated with cytokeratin filaments. This period is characterized by the initiation of differentiation of the basal cells, maturation of the basement membrane zone as well as accentuated formation of selected cellular junctions. NF1 tumor suppressor may function in the regulation of epidermal histogenesis via controlling the organization of the keratin cytoskeleton during the assembly of desmosomes and hemidesmosomes.