A Presenilin-2-ARF4 trafficking axis modulates Notch signaling during epidermal differentiation
| Autor: | H. Amalia Pasolli, Ellen J. Ezratty, Elaine Fuchs |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Keratinocytes Embryo Nonmammalian Cellular differentiation Organogenesis Amino Acid Motifs Notch signaling pathway Biology Presenilin Article 03 medical and health sciences Mice 0302 clinical medicine Genes Reporter Presenilin-2 Presenilin-1 Basal body Animals Small GTPase Cilia 10. No inequality Cells Cultured Research Articles integumentary system Receptors Notch ADP-Ribosylation Factors Cilium Cell Differentiation Cell Biology Basal Bodies Cell biology Protein Transport 030104 developmental biology Notch proteins Epidermal Cells Signal transduction Epidermis 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Ciliogenesis in differentiating epidermal cells correlates with activation of Notch signaling, which requires Presenilin-2 targeting to basal bodies/cilia. Ezratty et al. show that the GTPase ARF4 regulates Presenilin-2 localization and subsequent Notch-dependent differentiation, suggesting that polarized exocytosis to basal bodies spatially regulates Notch signaling during skin development. How primary cilia impact epidermal growth and differentiation during embryogenesis is poorly understood. Here, we show that during skin development, Notch signaling occurs within the ciliated, differentiating cells of the first few suprabasal epidermal layers. Moreover, both Notch signaling and cilia disappear in the upper layers, where key ciliary proteins distribute to cell–cell borders. Extending this correlation, we find that Presenilin-2 localizes to basal bodies/cilia through a conserved VxPx motif. When this motif is mutated, a GFP-tagged Presenilin-2 still localizes to intercellular borders, but basal body localization is lost. Notably, in contrast to wild type, this mutant fails to rescue epidermal differentiation defects seen upon Psen1 and 2 knockdown. Screening components implicated in ciliary targeting and polarized exocytosis, we provide evidence that the small GTPase ARF4 is required for Presenilin basal body localization, Notch signaling, and subsequent epidermal differentiation. Collectively, our findings raise the possibility that ARF4-dependent polarized exocytosis acts through the basal body–ciliary complex to spatially regulate Notch signaling during epidermal differentiation. |
| Databáze: | OpenAIRE |
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