| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-139 |
Sentence |
denotes |
The novel membrane protein TMEM59 modulates complex glycosylation, cell surface expression, and secretion of the amyloid precursor protein. |
| T2 |
140-344 |
Sentence |
denotes |
Ectodomain shedding of the amyloid precursor protein (APP) by the two proteases alpha- and beta-secretase is a key regulatory event in the generation of the Alzheimer disease amyloid beta peptide (Abeta). |
| T3 |
345-450 |
Sentence |
denotes |
At present, little is known about the cellular mechanisms that control APP shedding and Abeta generation. |
| T4 |
451-558 |
Sentence |
denotes |
Here, we identified a novel protein, transmembrane protein 59 (TMEM59), as a new modulator of APP shedding. |
| T5 |
559-632 |
Sentence |
denotes |
TMEM59 was found to be a ubiquitously expressed, Golgi-localized protein. |
| T6 |
633-719 |
Sentence |
denotes |
TMEM59 transfection inhibited complex N- and O-glycosylation of APP in cultured cells. |
| T7 |
720-940 |
Sentence |
denotes |
Additionally, TMEM59 induced APP retention in the Golgi and inhibited Abeta generation as well as APP cleavage by alpha- and beta-secretase cleavage, which occur at the plasma membrane and in the endosomes, respectively. |
| T8 |
941-1088 |
Sentence |
denotes |
Moreover, TMEM59 inhibited the complex N-glycosylation of the prion protein, suggesting a more general modulation of Golgi glycosylation reactions. |
| T9 |
1089-1296 |
Sentence |
denotes |
Importantly, TMEM59 did not affect the secretion of soluble proteins or the alpha-secretase like shedding of tumor necrosis factor alpha, demonstrating that TMEM59 did not disturb the general Golgi function. |
| T10 |
1297-1473 |
Sentence |
denotes |
The phenotype of TMEM59 transfection on APP glycosylation and shedding was similar to the one observed in cells lacking conserved oligomeric Golgi (COG) proteins COG1 and COG2. |
| T11 |
1474-1569 |
Sentence |
denotes |
Both proteins are required for normal localization and activity of Golgi glycosylation enzymes. |
| T12 |
1570-1823 |
Sentence |
denotes |
In summary, this study shows that TMEM59 expression modulates complex N- and O-glycosylation and suggests that TMEM59 affects APP shedding by reducing access of APP to the cellular compartments, where it is normally cleaved by alpha- and beta-secretase. |