PMID:15474363

Citation	Hébert, SS, Serneels, L, Dejaegere, T, Horré, K, Dabrowski, M, Baert, V, Annaert, W, Hartmann, D and De Strooper, B (2004) Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol. Dis. 17:260-72
Abstract	Gamma-secretase is a high molecular weight protein complex composed of four subunits, namely, presenilin (PS; 1 or 2), nicastrin, anterior pharynx defective-1 (Aph-1; A or B), and presenilin enhancer-2 (Pen-2), and is responsible for the cleavage of a number of type-1 transmembrane proteins. A fundamental question is whether different gamma-secretase complexes exist in vivo. We demonstrate here by in situ hybridization and by Northern and Western blotting that the gamma-secretase components are widely distributed in all tissues investigated. The expression of the different subunits seems tightly coregulated. However, some variation in the expression of the Aph-1 proteins is observed, Aph-1A being more general and abundantly distributed than Aph-1B. The previously uncharacterized rodent-specific Aph-1C mRNA is highly expressed in the kidney and testis but not in brain or other tissues, indicating some tissue specificity for the Aph-1 component of the gamma-secretase complex. Blue-native electrophoresis revealed size heterogeneity of the mature gamma-secretase complex in various tissues. Using co-immunoprecipitations and blue-native electrophoresis at endogenous protein levels, we find evidence that several independent gamma-secretase complexes can coexist in the same cell type. In conclusion, our results suggest that gamma-secretase is a heterogeneous family of protein complexes widely expressed in the adult organism.
Links	PubMed Online version:10.1016/j.nbd.2004.08.002
Keywords	Amino Acid Sequence; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Blotting, Western; Cell Line; Chromosome Segregation; Endopeptidases/chemistry; Endopeptidases/metabolism; HeLa Cells; Humans; Isoenzymes/metabolism; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Knockout; Molecular Sequence Data; Molecular Weight; Peptide Hydrolases; Presenilin-1; Presenilin-2; Protein Isoforms/metabolism; RNA, Messenger/metabolism; Tissue Distribution; Transfection
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.