Why the study?
The physiological roles and mechanisms underlying presenilins' multiple biological functions beyond gamma-secretase activity remain unclear due to early embryonic lethality of PS1/2 null mice.
Population
Cells derived from PS1/2 null blastocysts and wild type controls
Comparison
Expression of PS1 or PS2 versus intracellular form of Notch1 in PS1/2 null cells
Design
Proteomic approach in preclinical cell model
Key result
Presenilin deficiency in cells leads to abnormal intracellular retention of caveolin 1 and loss of caveolae, demonstrating that presenilins are required for caveolin 1 transport to the plasma membrane.
Authors
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PS1/2 double knockout causes embryonic lethality; leaves open presenilin roles in adult cardiovascular and neurodegenerative models.
Presenilins play a critical role in caveolae formation by regulating the intracellular transport of caveolin 1 to the plasma membrane.
Wood et al. (2004) studied Alzheimer's disease. Presenilin deficiency (PS1/2 null cells) vs. Wild type controls was evaluated on Caveolin 1 localization and caveolae formation. Presenilin deficiency in cells leads to abnormal intracellular retention of caveolin 1 and loss of caveolae, demonstrating that presenilins are required for caveolin 1 transport to the plasma membrane.
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