Presenilin-dependent Processing and Nuclear Function of γ-Protocadherins
| Autor: | Nathalie Véron, Marcus Frank, Ingrid G. Haas, Rolf Kemler |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cadherin Related Proteins
Protocadherin Biology Kidney Transfection Biochemistry Presenilin Cell Line Mice Cell surface receptor Chlorocebus aethiops Endopeptidases Presenilin-2 Presenilin-1 Extracellular Animals Aspartic Acid Endopeptidases Humans Protease Inhibitors Molecular Biology Cadherin Membrane Proteins Dipeptides Cell Biology Fibroblasts Cadherins Molecular biology Matrix Metalloproteinases Recombinant Proteins Transmembrane protein Cell biology Membrane protein COS Cells biology.protein Carbamates Amyloid Precursor Protein Secretases Protein Processing Post-Translational Amyloid precursor protein secretase |
| Zdroj: | Journal of Biological Chemistry. 280:9313-9319 |
| ISSN: | 0021-9258 |
| Popis: | The recently described protocadherin gene clusters encode cadherin-related proteins, which are highly expressed in the vertebrate nervous system. Here, we report biochemical studies addressing proteolytic processing of gamma-protocadherins. These type-I transmembrane proteins are cleaved by a metalloproteinase in vivo, generating a soluble extracellular fragment and a carboxyl-terminal fragment associated with the cellular membrane. In addition, we show that the carboxyl-terminal fragment is a substrate for further cleavage mediated by presenilin. Consequently, accumulation of the fragment is found when gamma-secretase is inactivated either by the specific presenilin-inhibitor L685,458 or in double mutant murine embryonic fibroblasts lacking both presenilin genes. The gamma-secretase-generated carboxyl-terminal fragment is largely unstable but accumulates when proteasomal degradation is inhibited. Interestingly, the proteolytic fragment generated by gamma-secretase can localize to the nucleus. This is the first report providing experimental evidence for a cell surface receptor signaling function of protocadherins regulated by proteolytic events. |
| Databáze: | OpenAIRE |
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