Browse our anti-APH1A (APH1A) Antibodies

Human Anterior Pharynx Defective 1 Homolog A (C. Elegans) (APH1A) interaction partners

1. Using purified PSEN1/Aph1A gamma-secretase and the APPC99-3XFLAG substrate, authors show that substrate shortening progressively destabilizes the consecutive enzyme-substrate complexes that characterize the sequential gamma-secretase processing of APP; present a unifying model for how PSEN or APP mutations enhance amyloidogenic Abeta production, suggests that environmental factors may increase Alzheimer's Disease risk.

2. Data show that presenilin 1 (PS1)/anterior-pharynx-defective protein 1 (Aph1b), presenilin 2 (PS2)/Aph1aL, PS2/Aph1aS and PS2/anterior pharynx defective 1 homolog B (Aph1b) gamma-secretase produced amyloid beta peptide (Abeta) with a higher Abeta42+Abeta43-to-Abeta40 (Abeta42(43)/Abeta40) ratio than the other gamma-secretases.

3. Data show that presenilin 1 (PS1)-containing gamma-secretase complexes were targeted to the plasma membrane, whereas presenilin 2 (PS2)-containing ones were addressed to the trans-Golgi network, to recycling endosomes.

4. No statistically significant difference was detected either in APOE or APH-1a polymorphisms, not suggesting a strong susceptibility to the development of Alzheimer disease.

5. analysis of how the conformation of presenilin, Pen-2, Aph-1, and nicastrin affect the function and mechanism of gamma-secretase

6. A loss of PS/gamma-secretase function to cleave Abeta42(43) may initiate Alzheimer's disease.

7. We demonstrate that extending the transmembrane domain of the amyloid precursor protein-derived C99 substrate in proximity to the cytosolic face strongly influences gamma-secretase cleavage specificity.

8. The -980C/G polymorphism in APH-1A promoter confers risk of Alzheimer's disease

9. Coexpression of wild-type or S-palmitoylation-deficient APH1aL and nicastrin leads to marked stabilization of transgenic presenilin 1 in the brains of double-transgenic mice.

10. Endogenous Aph-1a and its proteolytic fragment have unique properties for cleavage control that may have implications for gamma-secretase regulation and intracellular distribution.

11. Co-overexpression of presenilin-1 or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 into the gamma-secretase complex

12. Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates

13. These data indicate that mammalian APH-1 (mAPH-1) along with presenilin 1 and nicastrin is probably a functional component of the gamma-secretase complex required for the intramembrane proteolysis of APP and Notch

14. APH-1 binds to presenilins and nicastrin and may play a role in maturation of presenilin-nicastrin complexes

15. Expression of APH-1A increases amyloid beta peptide levels and gamma-secretase activity.

16. APH-1 and the gamma-secretase complex bind to the transmembrane domain region of nicastrin

17. Six different polymorphisms have been determined but the polymorphisms in APH-1a/b coding regions are not linked to higher risk for Alzheimer disease in an Italian population.

18. APH-1 can be processed by several endoproteolytic events and generates a stable C-terminal fragment that associates with nicastrin

19. conserved transmembrane Gly122, Gly126, and Gly130 in the fourth transmembrane region of APH-1a are part of the membrane helix-helix interaction GXXXG motif and are essential for the stable association of APH-1aL with presenilin, nicastrin, and PEN-2

20. Only the combined overexpression of presenilin 1 and nicastrin together with APH-1a G122D facilitated the formation of a fully active gamma-secretase complex

Mouse (Murine) Anterior Pharynx Defective 1 Homolog A (C. Elegans) (APH1A) interaction partners

1. This work provides novel evidence for the role of miRNAs in memory formation and demonstrates the implication of APH1a protein in miRNA processing in the adult brain.

2. Prostaglandin I2 accumulation in neuronal cells activates PKA/CREB and JNK/c-Jun signaling pathways by phosphorylation, which results in APH-1alpha/1beta expression.

3. Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease gamma-secretase.

4. Abeta oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1alpha/-1beta (by >2.5-fold), which enhances the gamma-cleavage of APP and Abeta deposition during AD progression

5. Upregulation of PS1/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.

6. ficiency of beta-arrestin1 or inhibition of binding of beta-arrestin1 with APH-1 by small peptides reduced Abeta production without affecting Notch processing

7. Pen-2, as well as nicastrin and Aph-1alpha, is dispensable for presenilin endoproteolysis

8. Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates

9. presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, associate with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons

10. Our findings establish that APH-1a is the major mammalian APH-1 homolog present in presenilin-dependent gamma-secretase complexes during embryogenesis.

11. Nct has a critical role in the stability and proper intracellular trafficking of other components of the PS1/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1