CGC Bibliography Paper 5374

aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of BAPP, and presenilin protein accumulation.

Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D

Medline:

12110170

Citation:

Developmental Cell 3: 85-97 2002

Type:

ARTICLE

Genes:

aph-1 aph-2 glp-1 hop-1 lag-1 lag-2 lin-12 pen-2 sel-12

Abstract:

Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of PAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin. Human aph-1 and pen-2 partially rescue the C. elegans mutant phenotypes, demonstrating conserved functions. The human genes must be provided together to rescue the mutant phenotypes, and the inclusion of presenilin-1 improves rescue, suggesting that they interact closely with each other and with presenilin. RNAi-mediated inactivation of aph-1, pen-2, or nicastrin in cultured Drosophila cells reduces gamma-secretase cleavage of PAPP and Notch substrates and reduces the levels of processed presenilin. aph-1 and pen-2, like nicastrin, are required for the activity and accumulation of gamma-secretase.