Topology of phosphatidylserine synthase 1 in the endoplasmic reticulum membrane

Miyata, Noriyuki; Kuge, Osamu

doi:10.1002/pro.4182

Cited by 11 publications

(4 citation statements)

References 37 publications

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“…PSS1 topology and locations of previously reported missense pathogenic variants in PSS1. Topology is based on the 10 transmembrane‐helix model described by Miyata and Kuge (2021) and the boundaries of transmembranes designated by numbers is defined using the AF‐P48651‐F1‐model_v2. Pdb ( https://alphafold.ebi.ac.uk/entry/P48651).…”

Section: Discussionmentioning

confidence: 99%

De novo loss‐of‐function variant in PTDSS1 is associated with developmental delay

Gracie

Sengupta

Ferreira

et al. 2022

American J of Med Genetics Pt A

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Heterozygous de novo missense pathogenic variants in PTDSS1 that result in gain-offunction of phosphatidylserine synthase 1 are associated with Lenz-Majewski hyperostotic dwarfism (LMHD). We identified the novel heterozygous de novo variant p.(Leu137Phe) in PTDSS1 in a child with mild-to-moderate developmental delay.Skeletal survey revealed no evidence of LMHD in this patient. Functional assessment of the p.Leu137Phe variant was performed by overexpressing the mutant protein into HEK293 cells. Following C 14 -serine labeling and TLC analysis of lipids, we observed that the p.(Leu137Phe) variant displayed no catalytic activity compared to the wild-type enzyme. We conclude that p.(Leu137Phe) variant has decreased enzymatic activity and that is likely to be the etiology of the patient's symptoms given the gene's constraint in the population. This is the first report of the clinical phenotype seen in an individual with a heterozygous loss-of-function variant in PTDSS1. This phenotype is distinct from LMHD, which results from gain-of-function pathogenic variants in the same gene. Evaluation of the neurodevelopmental phenotype of additional individuals with loss-of-function variants in PTDSS1 is indicated to determine the spectrum of associated phenotypes.

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Section: Discussionmentioning

confidence: 99%

De novo loss‐of‐function variant in PTDSS1 is associated with developmental delay

Gracie

Sengupta

Ferreira

et al. 2022

American J of Med Genetics Pt A

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“…PSS1 catalyzes the exchange of choline from phosphatidylcholine for serine, whereas PSS2 performs the equivalent exchange with ethanolamine from phosphatidylethanolamine. In both cases, phosphatidylserine is obtained [34,35].…”

Section: Phospholipid Synthesis: Er and Mitochondria Cooperationmentioning

confidence: 95%

Endoplasmic Reticulum: A Hub in Lipid Homeostasis

Ventura¹,

Hernández‐Álvarez²

2023

Updates on Endoplasmic Reticulum

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Endoplasmic Reticulum (ER) is the largest and one of the most complex cellular structures, indicating its widespread importance and variety of functions, including synthesis of membrane and secreted proteins, protein folding, calcium storage, and membrane lipid biogenesis. Moreover, the ER is implicated in cholesterol, plasmalogen, phospholipid, and sphingomyelin biosynthesis. Furthermore, the ER is in contact with most cellular organelles, such as mitochondria, peroxisomes, Golgi apparatus, lipid droplets, plasma membrane, etc. Peroxisomes are synthesized from a specific ER section, and they are related to very-long-chain fatty acid metabolism. Similarly, lipid droplets are vital structures in lipid homeostasis that are formed from the ER membrane. Additionally, there is a specific region between the ER-mitochondria interface called Mitochondria-Associated Membranes (MAMs). This small cytosolic gap plays a key role in several crucial mechanisms from autophagosome synthesis to phospholipid transfer. Due to the importance of the ER in a variety of biological processes, alterations in its functionality have relevant implications for multiple diseases. Nowadays, a plethora of pathologies like non-alcoholic steatohepatitis (NASH), cancer, and neurological alterations have been associated with ER malfunctions.

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“…Specifically, PSS1 exchanges the choline of a PC for a serine, generating a PS molecule. However, PSS2 changes the ethanolamine of PE for a serine, also generating PS [11,14,15].…”

Section: Phospholipids Synthesismentioning

confidence: 99%

“…However, there is also another pathway like PC synthesis, whereby ethanolamine is phosphorylated by ethanolamine kinase and then converted to CDP-ethanolamine. CDP-ethanolamine is finally converted to PE when DAG is incorporated [14,15]. Although PC, PE, PS, PI, CL, and PG are all derived from phosphatidic acid, they follow different routes.…”

Section: Phospholipids Synthesismentioning

confidence: 99%

Phospholipid Membrane Transport and Associated Diseases

2022

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Phospholipids are the basic structure block of eukaryotic membranes, in both the outer and inner membranes, which delimit cell organelles. Phospholipids can also be damaged by oxidative stress produced by mitochondria, for instance, becoming oxidized phospholipids. These damaged phospholipids have been related to prevalent diseases such as atherosclerosis or non-alcoholic steatohepatitis (NASH) because they alter gene expression and induce cellular stress and apoptosis. One of the main sites of phospholipid synthesis is the endoplasmic reticulum (ER). ER association with other organelles through membrane contact sites (MCS) provides a close apposition for lipid transport. Additionally, an important advance in this small cytosolic gap are lipid transfer proteins (LTPs), which accelerate and modulate the distribution of phospholipids in other organelles. In this regard, LTPs can be established as an essential point within phospholipid circulation, as relevant data show impaired phospholipid transport when LTPs are defected. This review will focus on phospholipid function, metabolism, non-vesicular transport, and associated diseases.

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Topology of phosphatidylserine synthase 1 in the endoplasmic reticulum membrane

Cited by 11 publications

References 37 publications

De novo loss‐of‐function variant in PTDSS1 is associated with developmental delay

De novo loss‐of‐function variant in PTDSS1 is associated with developmental delay

Endoplasmic Reticulum: A Hub in Lipid Homeostasis

Phospholipid Membrane Transport and Associated Diseases

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