Transmembrane Protein 147 (TMEM147) Is a Novel Component of the Nicalin-NOMO Protein Complex

摘要: Nicastrin and its relative Nicalin (Nicastrin-like protein) are both members of larger protein complexes, namely γ-secretase the Nicalin-NOMO (Nodal modulator) complex. The complex, which contains Presenilin, APH-1, PEN-2 in addition to Nicastrin, catalyzes proteolytic cleavage transmembrane domain various proteins including β-amyloid precursor Notch. binding partner NOMO form a complex that was shown modulate Nodal signaling developing zebrafish embryos. Because experimentally determined native size (200–220 kDa) could not be satisfyingly explained by molecular masses (60 (130 kDa), we searched affinity-purified preparations for additional components low mass range. A ∼22-kDa isolated identified spectrometry as 147 (TMEM147), novel, highly conserved membrane with putative topology similar APH-1. Like NOMO, it localizes endoplasmic reticulum is expressed during early development. Overexpression knockdown experiments cultured cells demonstrate close relationship between three suggest they same We present evidence that, γ-secretase, assembly hierarchical starting formation intermediate. appears represent limiting factor regulating rate stabilizing other two components. conclude TMEM147 novel core component further emphasizing similarity γ-secretase.