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Published on: June 30, 2023
Tap42-associated protein phosphatase type 2A negatively regulates induction of autophagy
Tomohiro Yorimitsu1, Congcong He, Ke Wang
1Life Sciences Institute, Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Abstract:
Autophagy is a highly conserved degradative process in eukaryotic cells. This process plays an integral role in cellular physiology, and the levels of autophagy must be precisely controlled to prevent cellular dysfunction. The rapamycin-sensitive Tor kinase complex 1 (TORC1) has a major role in regulating the induction of autophagy; however, the regulatory mechanisms are not fully understood. Here, we find that Tap42 and protein phosphatase type 2A (PP2A) are involved in the regulation of autophagy in yeast. Temperature-sensitive mutant alleles of TAP42 revealed that autophagy was induced without inactivation of TORC1. Absence of the Tap42-interacting protein Tip41 abolished autophagy induction in the tap42 mutants, whereas overexpression of Tip41 activated autophagy. Furthermore, inactivation of PP2A stimulated autophagy and overexpression of a catalytic subunit of PP2A blocked rapamycin-induced autophagy. Our data support a model in which autophagy is negatively regulated by the Tap42-PP2A pathway.
Insights
Autophagy regulation in yeast involves Tap42 and protein phosphatase type 2A (PP2A). This pathway negatively controls autophagy, impacting cellular homeostasis and function.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Autophagy is a crucial cellular degradation process in eukaryotes, essential for maintaining cellular homeostasis.
- Precise control of autophagy levels is vital to prevent cellular dysfunction.
- The Tor kinase complex 1 (TORC1) regulates autophagy induction, but its mechanisms require further elucidation.
Purpose of the Study:
- To investigate the roles of Tap42 and protein phosphatase type 2A (PP2A) in regulating autophagy in yeast.
- To elucidate the molecular mechanisms by which Tap42 and PP2A influence autophagy induction.
Main Methods:
- Utilized temperature-sensitive mutant alleles of TAP42 to study autophagy induction.
- Examined the effect of Tip41 (a Tap42-interacting protein) on autophagy.
- Investigated the impact of PP2A inactivation and overexpression on autophagy.
Main Results:
- Autophagy was induced in tap42 mutants independently of TORC1 inactivation.
- Absence of Tip41 abolished autophagy induction in tap42 mutants, while Tip41 overexpression activated autophagy.
- PP2A inactivation stimulated autophagy, whereas PP2A overexpression inhibited rapamycin-induced autophagy.
Conclusions:
- The Tap42-PP2A pathway negatively regulates autophagy in yeast.
- These findings provide new insights into the complex regulatory network controlling autophagy.
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