2003
DOI: 10.1074/jbc.m209499200
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APH-1 Interacts with Mature and Immature Forms of Presenilins and Nicastrin and May Play a Role in Maturation of Presenilin·Nicastrin Complexes

Abstract: APH-1 and PEN-2 genes modulate the function of nicastrin and the presenilins in Caenorhabditis elegans.Preliminary studies in transfected mammalian cells overexpressing tagged APH-1 proteins suggest that this genetic interaction is mediated by a direct physical interaction. Using the APH-1 protein encoded on human chromosome 1 (APH-1 1 L; also known as APH-1a) as an archetype, we report here that endogenous forms of APH-1 are predominantly expressed in intracellular membrane compartments, including the endopla… Show more

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Cited by 151 publications
(172 citation statements)
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References 30 publications
(57 reference statements)
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“…[15][16][17] Similar to the results obtained with reduced Aph-1a expression, knockdown or knockout of either of the g-secretase components PS1, Nct or PEN-2 in the mouse led to affected levels of most of the nonsilenced g-secretase subunits. [18][19][20][21][22][23][24] In contrast, ablation of mouse PS2 expression had little effect on the expression levels of the other g-secretase components, 20,24,25 comparable to what we have observed in the I/I, II/II and III/III rat lines concerning the effect of reduced Aph-1b expression. 7 These findings suggest that PS2 and Aph-1b are somehow related.…”
Section: Discussionsupporting
confidence: 83%
“…[15][16][17] Similar to the results obtained with reduced Aph-1a expression, knockdown or knockout of either of the g-secretase components PS1, Nct or PEN-2 in the mouse led to affected levels of most of the nonsilenced g-secretase subunits. [18][19][20][21][22][23][24] In contrast, ablation of mouse PS2 expression had little effect on the expression levels of the other g-secretase components, 20,24,25 comparable to what we have observed in the I/I, II/II and III/III rat lines concerning the effect of reduced Aph-1b expression. 7 These findings suggest that PS2 and Aph-1b are somehow related.…”
Section: Discussionsupporting
confidence: 83%
“…Indeed, APH‐1 often combines with PEN‐2, nicastrin, and PS to generate an active form of γ‐secretase complex, which is responsible for the cleavage of β‐APP and for the deposition of Aβ (De Strooper, 2003). Once APH‐1 was found in C. elegans (Francis et al ., 2002), the APH‐1 complex was confirmed in several experimental models (Gu et al ., 2003; Luo et al ., 2003; Hansson et al ., 2004). Along these lines, APH‐1α/1β might also be involved in regulating the deposition of Aβ 1–42 in response to PGI 2 stimulation.…”
Section: Discussionmentioning
confidence: 99%
“…It is ideal for analysis and partial isolation of membrane Carbonate washed SY5Y membranes (500 lg) were run on BN/PAGE, proteins electroeluted from the PS complex region, treated with reducing sample buffer and analysed on 10% Tris/tricine gels using mini Biorad apparatus. PS1 NTF and full-length PS1 were detected with PS1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] antibody, PS1 loop antibody detected PS1 CTF, NCT was detected at 140 kDa, PEN-2 at 10 kDa and PS2 CTF detected with PS2 CTF antibody. Parallel poly(vinylidene difluoride) strips were also probed with APH 1a and 1b antibodies but APH-1 was not detected.…”
Section: Discussionmentioning
confidence: 99%
“…PEN-2 is a small double membrane-spanning protein with N-and C-termini facing the lumen [14]. APH-1 contains seven putative transmembrane domains and has a variety of isoforms with differing C-terminal domains; in humans, APH-1a long and short forms are encoded by a gene on chromosome 1 and APH-1b by chromosome 15 [15,16].…”
mentioning
confidence: 99%