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Published on: February 21, 2019
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P4-ATPase endosomal recycling relies on multiple retromer-dependent localization signals
Mariana Jiménez1, Claire K Kyoung1, Kateryna Nabukhotna1
1Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235.
Molecular Biology of the Cell
|August 7, 2024
Summary
Budding yeast P4-ATPases (lipid flippases) are recycled from endosomes to the Golgi via the retromer complex and Rcy1. Recycling defects cause mislocalization and loss of membrane asymmetry.
Area of Science:
- Cell Biology
- Membrane Biology
- Protein Trafficking
Background:
- Type IV P-type ATPases (P4-ATPases) are essential lipid flippases crucial for maintaining cellular membrane asymmetry.
- These proteins cycle between the Golgi, plasma membrane, and endosomes, but their retrieval from the endolysosomal system to the Golgi remains unclear.
Purpose of the Study:
- To investigate the mechanism of endosomal recycling for budding yeast P4-ATPases.
- To identify key factors and signals involved in P4-ATPase retrieval to the Golgi.
Main Methods:
- Utilized budding yeast as a model system.
- Investigated the roles of the retromer complex and Rcy1 in P4-ATPase trafficking.
- Characterized retromer sorting signals within P4-ATPases, including Dnf1 and Dnf2.
Main Results:
- Endosomal recycling of P4-ATPases is primarily mediated by the retromer complex and Rcy1.
- Impaired recycling leads to P4-ATPase mislocalization to the vacuole and loss of membrane asymmetry.
- Identified a novel retromer-dependent sorting signal, IPM[ST], in P4-ATPases that functions redundantly with other motifs.
Conclusions:
- Endosomal recycling is critical for the proper localization and function of P4-ATPases.
- The retromer complex and Rcy1 are key regulators of P4-ATPase membrane organization.
- Understanding these recycling pathways is essential for maintaining cellular homeostasis.
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