Membrane contact sites, gateways for lipid homeostasis

Lahiri, Sujoy; Toulmay, Alexandre; Prinz, William A.

doi:10.1016/j.ceb.2014.12.004

Cited by 132 publications

(117 citation statements)

References 46 publications

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“…The Ca 2+ -dependent role of E-Syts in the formation of MCSs between the ER and the plasma membrane, coupled with the proposed role for E-Syts in lipid transfer at these sites, suggests a function for localized Ca 2+ signals in establishing sites of lipid transfer. Ca 2+ exchange at ER -mitochondria MCSs, as discussed, is well established but MAMs have more recently been implicated in phospholipid transfer (reviewed in [29,61]), with transfer of phosphatidylserine (PS) from the ER to the mitochondria at MCSs recently demonstrated in yeast [28]. Finally, the role of oxysterol binding proteins in the formation of ER MCSs with the endocytic pathway suggests a role for these contacts in sterol transfer.…”

Section: Discussionmentioning

confidence: 95%

Calcium signaling at ER membrane contact sites

Burgoyne¹,

Patel

Eden³

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Communication between organelles is a necessary consequence of intracellular compartmentalization. Membrane contact sites (MCSs) are regions where the membranes of two organelles come into close apposition allowing exchange of small molecules and ions including Ca²⁺. The ER, the cell's major Ca²⁺ store, forms an extensive and dynamic network of contacts with multiple organelles. Here we review established and emerging roles of ER contacts as platforms for Ca²⁺ exchange and further consider a potential role for Ca²⁺ in the regulation of MCS formation. We additionally discuss the challenges associated with the study of MCS biology and highlight advances in microscopy-based solutions. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

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Section: Discussionmentioning

confidence: 95%

Calcium signaling at ER membrane contact sites

Burgoyne¹,

Patel

Eden³

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Subsequent studies have demonstrated that the ER interacts via tethering proteins with all other membranous organelles of the cell, and have identified a variety of functions for these contacts (7)(8)(9)(10)(11)(12). One major function is exchange of lipids between bilayers via lipid-transfer proteins (11,12,(21)(22)(23)(24). The occurrence of this mode of lipid transfer between membranes, which is independent of vesicular transport and membrane fusion, was first described in the late 1960s (25).…”

mentioning

confidence: 99%

Contacts between the endoplasmic reticulum and other membranes in neurons

Whiteus

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

412

501

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Close appositions between the membrane of the endoplasmic reticulum (ER) and other intracellular membranes have important functions in cell physiology. These include lipid homeostasis, regulation of Ca 2+ dynamics, and control of organelle biogenesis and dynamics. Although these membrane contacts have previously been observed in neurons, their distribution and abundance have not been systematically analyzed. Here, we have used focused ion beam-scanning electron microscopy to generate 3D reconstructions of intracellular organelles and their membrane appositions involving the ER (distance ≤30 nm) in different neuronal compartments. ER-plasma membrane (PM) contacts were particularly abundant in cell bodies, with large, flat ER cisternae apposed to the PM, sometimes with a notably narrow lumen (thin ER). Smaller ER-PM contacts occurred throughout dendrites, axons, and in axon terminals. ER contacts with mitochondria were abundant in all compartments, with the ER often forming a network that embraced mitochondria. Small focal contacts were also observed with tubulovesicular structures, likely to be endosomes, and with sparse multivesicular bodies and lysosomes found in our reconstructions. Our study provides an anatomical reference for interpreting information about interorganelle communication in neurons emerging from functional and biochemical studies.FIB-SEM | thin ER | Stim1 | spine apparatus | subsurface cisternae

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“…aintenance of the unique lipid composition of different eukaryotic cell membranes requires a concerted regulation of lipid synthesis and transport via vesicular trafficking and nonvesicular lipid transfer (1)(2)(3). Most lipids in the cell are synthesized in the endoplasmic reticulum (ER) or taken up from the outside for degradation and reutilization via the endo-lysosomal system.…”

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confidence: 99%

Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions

Sohn

Ivanova

Brown

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

123

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Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in the PTDSS1 gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.

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Membrane contact sites, gateways for lipid homeostasis

Cited by 132 publications

References 46 publications

Calcium signaling at ER membrane contact sites

Calcium signaling at ER membrane contact sites

Contacts between the endoplasmic reticulum and other membranes in neurons

Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions

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