| Autor: |
Tomita Taisuke, Tanaka Sayaka, Morohashi Yuichi, Iwatsubo Takeshi |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
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| Zdroj: |
Molecular Neurodegeneration, Vol 1, Iss 1, p 2 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1750-1326 |
| DOI: |
10.1186/1750-1326-1-2 |
| Popis: |
Abstract Background Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellular signaling. Considering γ-secretase inhibitors as therapeutics for Alzheimer's disease, understanding the physiologically and biologically important substrate for γ-secretase activity in brains is emerging issue. To elucidate the molecular mechanism and physiological role of γ-secretase, we screened candidate molecules for γ-secretase substrates. Results We show that ephrin-B1, that participates in cell-cell repulsive and attractive signaling together with its Eph receptor, constitutively undergoes ectodomain shedding and that the residual membrane-tethered fragment is sequentially cleaved by γ-secretase to release the intracellular domain. Furthermore, overexpression of membrane-tethered ephrin-B1 caused protrusion of numerous cellular processes consisted of F-actin, that required the preservation of the most C-terminal region of ephrin-B1. In contrast, soluble intracellular domain translocated into the nucleus and had no effect on cell morphology. Conclusion Our findings suggest that ephrin-B is a genuine substrate for γ-secretase and regulates the cytoskeletal dynamics through intramembrane proteolysis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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