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Ptc1p regulates cortical ER inheritance via Slt2p.
Yunrui Du1, Lee Walker, Peter Novick
1Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
Ptc1p and Nbp2p regulate endoplasmic reticulum (ER) inheritance in yeast by modulating the cell wall integrity (CWI) MAPK pathway. Loss of these proteins delays ER tubule delivery, a defect suppressed by inhibiting the CWI pathway.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Organelle inheritance, including endoplasmic reticulum (ER), mitochondria, and vacuoles, in yeast involves capturing tubular structures at the bud tip.
- Ptc1p, a serine/threonine phosphatase, is known to influence mitochondrial inheritance through an uncharacterized mechanism and is involved in both the high osmolarity glycerol (HOG) and cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathways.
Purpose of the Study:
- To elucidate the mechanism by which Ptc1p regulates endoplasmic reticulum (ER) inheritance.
- To investigate the role of the Ptc1p binding protein, Nbp2p, in ER inheritance.
- To determine the involvement of MAPK pathways in ER inheritance regulated by Ptc1p and Nbp2p.
Main Methods:
- Investigated ER inheritance defects in yeast mutants lacking Ptc1p (ptc1Δ) or Nbp2p (nbp2Δ).
- Assessed the levels of phosphorylated Slt2p, the MAPK of the CWI pathway, in these mutants.
- Examined the effect of deleting Slt2p or inhibiting the CWI pathway on ER inheritance in ptc1Δ and nbp2Δ mutants.
Main Results:
- Loss of Ptc1p or Nbp2p resulted in a significant delay in ER tubule delivery to daughter cells.
- The absence of Ptc1p or Nbp2p led to a marked increase in phosphorylated Slt2p levels.
- Deletion of Slt2p or sorbitol-induced inhibition of the CWI pathway suppressed the ER inheritance defects observed in ptc1Δ and nbp2Δ mutants.
Conclusions:
- Ptc1p and Nbp2p are crucial regulators of ER inheritance in yeast.
- ER inheritance is controlled via the CWI MAPK pathway, specifically by modulating Slt2p activity.
- These findings reveal a novel link between phosphatase activity, MAPK signaling, and organelle inheritance.
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