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Reticulons bind sphingolipids to activate the endoplasmic reticulum cell cycle checkpoint, the ER surveillance
Francisco Piña1, Bing Yan2, Junjie Hu2
1Division of Biological Sciences, Molecular Biology Section, University of California, San Diego, NSB#1, Rm. 5328, 9500 Gilman Drive, San Diego, CA 92093-0377, USA.
Cell Reports
|November 18, 2023
Summary
Reticulon 1 (Rtn1) and Yop1 proteins bind phytosphingosine (PHS) during ER stress, blocking ER inheritance. Mutating PHS-binding sites prevents this block, revealing a conserved stress response mechanism.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) requires precise inheritance for cellular function.
- The ER stress surveillance (ERSU) pathway monitors ER health and inheritance.
- Reticulon 1 (Rtn1) and Yop1 are known proteins involved in shaping the ER.
Purpose of the Study:
- To investigate the role of Rtn1 and Yop1 in ER inheritance during ER stress.
- To identify the molecular mechanism by which Rtn1 and Yop1 influence ER inheritance.
Main Methods:
- Analysis of sphingolipid-binding motifs in Rtn1 and Yop1.
- Investigating the interaction between Rtn1/Yop1 and phytosphingosine (PHS).
- Studying the effect of PHS binding on ER tubule localization and ER inheritance.
Main Results:
- Rtn1 and Yop1 possess sphingolipid-binding motifs that recognize ER-stress-induced PHS.
- PHS binding causes Rtn1/Yop1 accumulation on ER tubules, misdirecting ER inheritance to bud scars.
- Mutations in PHS-binding motifs abolish PHS recognition and prevent the ER inheritance block.
Conclusions:
- Sphingolipid binding to Rtn1 and Yop1 is a novel mechanism for ER stress response.
- This PHS-binding interaction regulates ER inheritance.
- The conserved nature of these motifs suggests an evolutionarily ancient role in cellular stress adaptation.
Keywords:
CP: Cell biologyERER inheritanceER stressER surveillancecell cycle checkpointcytokinesis blockendoplasmic reticulumphytosphingosinereticulonssphingolipidsMore Related Videos
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