scholarly journals Tricalbin proteins regulate plasma membrane phospholipid homeostasis

2021 ◽  
Author(s):  
Ffion B Thomas ◽  
Deike J Omnus ◽  
Jakob M Bader ◽  
Gary HC Chung ◽  
Nozomu Kono ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Family Members ◽  
Lipid Transfer ◽  
Membrane Stress ◽  
Lipid Transfer Proteins ◽  
Induced Membrane ◽  
Phospholipid Asymmetry ◽  
Evolutionarily Conserved ◽  
Essential Function ◽  
Plasma Membrane Phospholipid

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the endoplasmic reticulum and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain unclear. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also promote the recruitment of Pkh1, a stress-activated protein kinase required for PM integrity. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We suggest that phospholipid regulation is an ancient essential function of E-Syt family members in PM integrity.

scholarly journals Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tomoki Naito ◽  
Bilge Ercan ◽  
Logesvaran Krshnan ◽  
Alexander Triebl ◽  
Dylan Hong Zheng Koh ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Intracellular Transport ◽  
Lipid Transfer Protein ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transfer Protein ◽  
Major Structural Component ◽  
Acute Increase ◽  
Transport Transition ◽  
Plasma Membrane Cholesterol

Cholesterol is a major structural component of the plasma membrane (PM). The majority of PM cholesterol forms complexes with other PM lipids, making it inaccessible for intracellular transport. Transition of PM cholesterol between accessible and inaccessible pools maintains cellular homeostasis, but how cells monitor the accessibility of PM cholesterol remains unclear. We show that endoplasmic reticulum (ER)-anchored lipid transfer proteins, the GRAMD1s, sense and transport accessible PM cholesterol to the ER. GRAMD1s bind to one another and populate ER-PM contacts by sensing a transient expansion of the accessible pool of PM cholesterol via their GRAM domains. They then facilitate the transport of this cholesterol via their StART-like domains. Cells that lack all three GRAMD1s exhibit striking expansion of the accessible pool of PM cholesterol as a result of less efficient PM to ER transport of accessible cholesterol. Thus, GRAMD1s facilitate the movement of accessible PM cholesterol to the ER in order to counteract an acute increase of PM cholesterol, thereby activating non-vesicular cholesterol transport.

scholarly journals ORP1L, ORP1S, and ORP2: Lipid Sensors and Transporters

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642095681
Author(s):  
Yvette C. Aw ◽  
Andrew J. Brown ◽  
Jia-Wei Wu ◽  
Hongyuan Yang
Keyword(s):  
Plasma Membrane ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Lipid Transfer ◽  
Cholesterol Trafficking ◽  
Lipid Transfer Proteins ◽  
Oxysterol Binding Protein ◽  
Membrane Contact ◽  
Related Proteins ◽  
Lipid Sensors

Lipid transfer proteins are crucial for intracellular cholesterol trafficking at sites of membrane contact. In the OSBP/ORPs (oxysterol binding protein and OSBP-related proteins) family of lipid transfer proteins, ORP1L, ORP1S and ORP2 play important roles in cholesterol transport. ORP1L is an endosome/lysosome-anchored cholesterol sensor which may also move cholesterol bidirectionally at the interface between the endoplasmic reticulum and the endosome/lysosome. ORP2 delivers cholesterol to the plasma membrane, driven by PI(4,5)P2 hydrolysis. ORP1S may also transport cholesterol to the plasma membrane, although it is unclear if phosphoinositides are involved. The source of cholesterol delivered to the plasma membrane by ORP1S and ORP2 remains unclear. This review summarises the roles of these proteins in maintaining cellular cholesterol homeostasis and in human disease.

scholarly journals Regulation of Plasma Membrane Sterol Homeostasis by Nonvesicular Lipid Transport

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110424
Author(s):  
Dylan Hong Zheng Koh ◽  
Yasunori Saheki
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Structural Integrity ◽  
Critical Role ◽  
Lipid Transfer ◽  
Fusion Reactions ◽  
Lipid Transfer Proteins ◽  
Membrane Budding ◽  
Mode Of Transport

Sterol contributes to the structural integrity of cellular membranes and plays an important role in the regulation of cell signaling in eukaryotes. It is either produced in the endoplasmic reticulum or taken up from the extracellular environment. In most eukaryotic cells, however, the majority of sterol is enriched in the plasma membrane. Thus, the transport of sterol between the plasma membrane and other organelles, including the endoplasmic reticulum, is crucial for maintaining sterol homeostasis. While vesicular transport that relies on membrane budding and fusion reactions plays an important role in bulk sterol transport, this mode of transport is slow and non-selective. Growing evidence suggests a critical role of nonvesicular transport mediated by evolutionarily conserved families of lipid transfer proteins in more rapid and selective delivery of sterol. Some lipid transfer proteins act primarily at the sites of contacts formed between the endoplasmic reticulum and other organelles or the plasma membrane without membrane fusion. In this review, we describe the similarities and differences of sterol biosynthesis and uptake in mammals and yeast and discuss the role of their lipid transfer proteins in maintaining plasma membrane sterol homeostasis.

scholarly journals Osh6 requires Ist2 for localization to the ER-PM contacts and efficient phosphatidylserine transport

2020 ◽  
Author(s):  
Juan Martín D’Ambrosio ◽  
Véronique Albanèse ◽  
Nicolas-Frédéric Lipp ◽  
Lucile Fleuriot ◽  
Delphine Debayle ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Lipid Transport ◽  
Membrane Targeting ◽  
Lipid Transfer ◽  
Binding Region ◽  
Cellular Functions ◽  
Lipid Transfer Proteins ◽  
Contact Sites ◽  
Binding Surface

AbstractOsh6 and Osh7 are lipid transfer proteins (LTPs) that move phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM). High PS level at the PM is key for many cellular functions. Intriguingly, Osh6/7 localize to ER-PM contact sites, although they lack membrane-targeting motifs, in contrast to multidomain LTPs that both bridge membranes and convey lipids. We show that Osh6 localization to contact sites depends on its interaction with the cytosolic tail of the ER-PM tether Ist2, a homologue of TMEM16 proteins. We identify a motif in the Ist2 tail, conserved in yeasts, as the Osh6-binding region, and we map an Ist2-binding surface on Osh6. Mutations in the Ist2 tail phenocopy osh6Δ osh7Δ deletion: they decrease cellular PS levels, and block PS transport to the PM. Our study unveils an unexpected partnership between a TMEM16-like protein and a soluble LTP, which together mediate lipid transport at contact sites.

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