2007
DOI: 10.1038/sj.embor.7401027
|View full text |Cite
|
Sign up to set email alerts
|

Endoplasmic reticulum retention of the γ‐secretase complex component Pen2 by Rer1

Abstract: γ‐Secretase is involved in the production of amyloid β‐peptide, which is the principal component of amyloid plaques in the brains of patients with Alzheimer disease. γ‐Secretase is a complex composed of presenilin (PS), nicastrin, anterior pharynx‐defective phenotype 1 (Aph1) and PS enhancer 2 (Pen2). We previously proposed a mechanism of complex assembly by which unassembled subunits are retained in the endoplasmic reticulum (ER) and only the fully assembled complex is exported from the ER. We have now identi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1

Citation Types

7
85
2
4

Year Published

2009
2009
2024
2024

Publication Types

Select...
5
2

Relationship

1
6

Authors

Journals

citations
Cited by 79 publications
(99 citation statements)
references
References 19 publications
(37 reference statements)
7
85
2
4
Order By: Relevance
“…This finding was corroborated by immunohistochemical colocalization analysis in skeletal muscle (Fig. S1), and it is consistent with previous findings in other cell types (7,8). In C2C12 cells, Rer1 expression increased strongly during differentiation, concomitant with the up-regulation of AChRα ( Fig.…”
Section: Resultssupporting
confidence: 80%
See 1 more Smart Citation
“…This finding was corroborated by immunohistochemical colocalization analysis in skeletal muscle (Fig. S1), and it is consistent with previous findings in other cell types (7,8). In C2C12 cells, Rer1 expression increased strongly during differentiation, concomitant with the up-regulation of AChRα ( Fig.…”
Section: Resultssupporting
confidence: 80%
“…Like the KDEL receptor (KDELR), Rer1 is localized in early secretory compartments, mainly the cis-Golgi (7). Recently, mammalian Rer1 was shown to be involved in retaining/retrieving unassembled Pen2 (8) and Nicastrin (9), both membrane protein constituents of the γ-secretase, to the ER. Here, we provide in vitro and in vivo evidence that Rer1 blocks the surface exposure of unassembled AChRα subunits and that reduced expression of Rer1 affects the size of neuromuscular synapses.…”
mentioning
confidence: 99%
“…6A, top panels). Considering the earlier reported roles for RER1 in regulating ␥-secretase assembly (41,42), it seems insufficient to explain our observation on the decreased levels of sAPP release, which is dependent on cleavage by ␣-or ␤-secretase. In addition, the Western blot analysis revealed that the steady-state levels of mature APP were significantly decreased and immature APP increased by RER1 overexpression (Fig.…”
Section: Resultscontrasting
confidence: 52%
“…Previous studies have suggested that RER1 competes with APH1 for NCT binding and negatively regulates the assembly of ␥-secretase (41); or that RER1 binds to PEN2 (42). However, we find that RER1 co-immunoprecipitates with the ␥-secretase complex, as opposed to selectively binding individual disassociated components of the complex.…”
Section: Discussioncontrasting
confidence: 53%
See 1 more Smart Citation