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  γ-Protocadherins, presenilin-mediated release of C-terminal fragment promotes locus expression

Hambsch, B., Grinevich, V., Seeburg, P. H., & Schwarz, M. K. (2005). γ-Protocadherins, presenilin-mediated release of C-terminal fragment promotes locus expression. The Journal of Biological Chemistry, 280(16), 15888-15897. doi:10.1074/jbc.M414359200.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-7034-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-7035-D
Genre: Journal Article
Alternative Title : Gamma-Protocadherins, presenilin-mediated release of C-terminal fragment promotes locus expression

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JBiolChem_280_2005_15888.pdf (Any fulltext), 716KB
 
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 Creators:
Hambsch, Boris1, Author              
Grinevich, Valery1, Author              
Seeburg, Peter H.1, Author              
Schwarz, Martin K.1, Author              
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 Abstract: γ-Protocadherins (γ-pcdhs) are type I membrane-spanning glycoproteins, widely expressed in the mammal and required for survival. These cell adhesion molecules are expressed from a complex locus comprising 22 functional variable exons arranged in tandem, each encoding extracellular, transmembrane and intracellular sequence, and three exons for an invariant C-terminal domain (γ-ICD). However, the signaling mechanisms that lie downstream of γ-pcdhs have not been elucidated. Here we report that γ-pcdhs are subject to presenilin-dependent intramembrane cleavage (PS-IP), accompanied by shedding of the extracellular domain. The cleaved intracellular domain (γ-ICD) translocates to the cell nucleus and was detected in subsets of cortical neurons. Notably, gene-targeted mice lacking functional γ-ICD sequence showed severely reduced γ-pcdh mRNA levels and neonatal lethality. Most importantly, inhibition of γ-secretase decreased γ-pcdh locus expression. Luciferase reporter assays demonstrated that γ-pcdh promoter activity is increased by γ-ICD. These results reveal an intracellular signaling mechanism for γ-pcdhs and identify a novel vital target for the γ-secretase complex.

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Language(s): eng - English
 Dates: 2004-12-212005-02-112005-02-112005-04-22
 Publication Status: Published in print
 Pages: 10
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 Table of Contents: -
 Rev. Method: Peer
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Title: The Journal of Biological Chemistry
  Alternative Title : J. Biol. Chem.
Source Genre: Journal
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Publ. Info: Baltimore, etc. : American Society for Biochemistry and Molecular Biology [etc.]
Pages: - Volume / Issue: 280 (16) Sequence Number: - Start / End Page: 15888 - 15897 Identifier: -