FIGURE 4.

PS1 L435F and neighboring mutations inhibit γ-secretase-dependent cleavage of endogenous N-cadherin. WT and mutant PS1 were transiently expressed in PS-null MEFs. Disappearance of N-cadherin (N-Cad) CTF1 was monitored as a measure of γ-secretase activity toward endogenous substrate. Con (A) and vector (B) indicate transfection with empty rather than PS1-expressing vector. A, endogenous levels of full-length (FL) N-Cad and CTF1 were detected with antibody recognizing a sequence in the intracellular domain. IB, immunoblot; α-tub, α-tubulin. Con, control. B, quantification of N-Cad CTF1 levels is shown. CTF1 levels were normalized to α-tubulin and expressed as % of control (empty vector) levels. Data are the means of three independent experiments (*, p < 0.05 compared with transfection with empty vector; n = 3).