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Examining requirement for formation of functional Presenilin proteins and their processing events in vivo
Author(s) -
Barakat Ala,
Mercer Bettie,
Cooper Emilie,
Chung HuiMin
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20475
Subject(s) - presenilin , transmembrane protein , biology , microbiology and biotechnology , cytosol , cleavage (geology) , protein subunit , transmembrane domain , protease , in vivo , drosophila melanogaster , transgene , biochemistry , genetics , enzyme , gene , receptor , medicine , paleontology , disease , pathology , fracture (geology) , alzheimer's disease
Presenilin (Psn) is a multipass transmembrane protein that functions as the catalytic subunit of γ‐secretase for mediating intramembrane cleavage of type 1 transmembrane proteins. Normally active Psn is in the form of a heterodimer composed by its N‐terminal and C‐terminal fragments that are generated from a Presenilinase‐mediated endoproteolytic cleavage within its large cytosolic loop during assembly of the protease complex. Using the Psn forms that either bypass or disable Presenilinase‐mediated endoproteolysis, and a Psn form that has most of the large cytosolic loop deleted, we have established an in vivo system to enable investigations of Psn functional domains in Drosophila . We show that the Presenilinase‐mediated endoproteolytic event is not essential for producing Psn activity during animal development, and is regulated by integrity of the large cytosolic loop of Psn in Drosophila . The Psn transgenic flies described here could be applied to a broad range of studies on Psn functioning and its related γ‐secretase activity at any developmental stage. genesis 47:161–168, 2009. © 2009 Wiley‐Liss, Inc.