| First Author | H?bert SS | Year | 2004 |
| Journal | Neurobiol Dis | Volume | 17 |
| Issue | 2 | Pages | 260-72 |
| PubMed ID | 15474363 | Mgi Jnum | J:93093 |
| Mgi Id | MGI:3055708 | Doi | 10.1016/j.nbd.2004.08.002 |
| Citation | Hebert SS, et al. (2004) Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneity. Neurobiol Dis 17(2):260-72 |
| abstractText | 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. |
