ER-to-Plasma Membrane Tethering Proteins Regulate Cell Signaling and ER Morphology

Manford, Andrew G.; Stefan, Christopher J.; Yuan, Helen L.; MacGurn, Jason A.; Emr, Scott D.

doi:10.1016/j.devcel.2012.11.004

Cited by 476 publications

(709 citation statements)

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“…Recently, a plant homolog of the yeast Scs2 protein, VAP27, was reported to localize at Arabidopsis ER-PM contact sites, identifying the first molecular components of such sites in plants (Wang et al, 2014). The Arabidopsis SYT1 contains the modular structure typical of tricalbins and E-Syts (Craxton, 2010;Yamazaki et al, 2010), is enriched at ER-PM subdomains, and similar to yeast, where Scs2 and Tcbs interact (Manford et al, 2012), it colocalizes with the ER-PM contact sites marker VAP27. Together, these results support the notion that an ER-PM tethering mechanism similar to that in yeast and mammals exists in plants.…”

Section: Syt1 Is a Plant Er-pm Phospholipid Binding Anchormentioning

confidence: 99%

“…In yeast, three conserved protein families have been identified as ER-PM tethers: INCREASED SODIUM TOLERANCE2 (related to the mammalian anoctamin family of ion channels), the VAP proteins SUPPRESSOR OF CHOLINE SENSITIVITY2 (Scs2) and Scs22 and the tricalbin (Tcb) proteins Tcb1 to Tcb3 (orthologs of the extended synaptotagmin-like proteins E-Syt1 to E-Syt3 in mammals; Manford et al, 2012). Recently, a plant homolog of the yeast Scs2 protein, VAP27, was reported to localize at Arabidopsis ER-PM contact sites, identifying the first molecular components of such sites in plants (Wang et al, 2014).…”

Section: Syt1 Is a Plant Er-pm Phospholipid Binding Anchormentioning

confidence: 99%

“…SYT1 belongs to a five-member family in Arabidopsis and shares a common modular structure with different members of the mammalian extended synaptotagmins (E-Syts) and yeast (Saccharomyces cerevisiae) tricalbins families of organelle tethers (Manford et al, 2012;Fig. 1A;Supplemental Fig.…”

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The Arabidopsis Synaptotagmin1 Is Enriched in Endoplasmic Reticulum-Plasma Membrane Contact Sites and Confers Cellular Resistance to Mechanical Stresses

et al. 2015

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Eukaryotic endoplasmic reticulum (ER)-plasma membrane (PM) contact sites are evolutionarily conserved microdomains that have important roles in specialized metabolic functions such as ER-PM communication, lipid homeostasis, and Ca 2+ influx. Despite recent advances in knowledge about ER-PM contact site components and functions in yeast (Saccharomyces cerevisiae) and mammals, relatively little is known about the functional significance of these structures in plants. In this report, we characterize the Arabidopsis (Arabidopsis thaliana) phospholipid binding Synaptotagmin1 (SYT1) as a plant ortholog of the mammal extended synaptotagmins and yeast tricalbins families of ER-PM anchors. We propose that SYT1 functions at ER-PM contact sites because it displays a dual ER-PM localization, it is enriched in microtubule-depleted regions at the cell cortex, and it colocalizes with Vesicle-Associated Protein27-1, a known ER-PM marker. Furthermore, biochemical and physiological analyses indicate that SYT1 might function as an electrostatic phospholipid anchor conferring mechanical stability in plant cells. Together, the subcellular localization and functional characterization of SYT1 highlights a putative role of plant ER-PM contact site components in the cellular adaptation to environmental stresses.

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Section: Syt1 Is a Plant Er-pm Phospholipid Binding Anchormentioning

confidence: 99%

Section: Syt1 Is a Plant Er-pm Phospholipid Binding Anchormentioning

confidence: 99%

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The Arabidopsis Synaptotagmin1 Is Enriched in Endoplasmic Reticulum-Plasma Membrane Contact Sites and Confers Cellular Resistance to Mechanical Stresses

et al. 2015

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“…Contain TULIP lipid transfer domains § . [70] 494 20 bridging proteins/complexes proposed to have tether properties, categorised by extent to 495 which they meet two overall criteria: (i) their effect on contact structure …”

Section: Ermitochondria (Vertebrates)mentioning

confidence: 99%

“…Instead they contain domains that strongly point to other functions. 262Clear examples of this can be found among six bridging proteins at ER-plasma membranes 263 10 contacts in yeast that have been deleted to reduce cortical ER by 90% [70]. Only the yeast VAP 264 homologs Scs2/22p are clearly responsible for tethering, but there is no obvious effect on the 265 extent of cortical ER with single deletions of the other bridging proteins: tricalbins and Ist2p (Table 266 1).…”

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confidence: 99%

Piecing Together the Patchwork of Contact Sites

Gatta¹,

Levine²

2017

Trends in Cell Biology

150

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7Contact sites are places where two organelles join together to carry out a shared activity requiring 8 non--vesicular communication. A large number of contact sites have been discovered, and almost 9 any two organelles can contact each other. General rules about contacts include constraints on 10 bridging proteins, with only a minority of bridges physically creating contacts by acting as 11 "tethers". The downstream effects of contacts include changing the physical behaviour of 12 organelles, and also forming biochemically heterogeneous sub--domains. However, some functions 13 typically localised to contact sites, such as lipid transfer, have no absolute requirement to be 14 situated there. Therefore, the key aspect of contacts is the directness of communication, which 15 allows metabolic channelling and collective regulation. and Rouiller [1]. Afterwards contact sites were largely overlooked for 50 years [2], and are still 31missing from text books. The last decade has seen much progress, and there are many excellent 32 reviews that describe these developments as a whole [3,4], or at a single contact site [5] or for one 33 family of components [6]. This article has a dual focus: in this section we describe how almost 34 every pair of organelles now appears to form contacts (Figure 1, Key Figure); later we make 35 general inferences about contact site function. 36 37 Contacts formed by mitochondria, a second intracellular network 38Early on the ER appeared as a common partner to most other organelles, including mitochondria, 39 plasma membrane, endosomes/phagosomes/lysosomes, Golgi apparatus and lipid droplets. This 40 led us to suggest a model that all organelles had constitutive contacts with the ER, which acts as a 41 pan-cellular conduit for small metabolites such as Ca 2+ and lipids [2]. However, the demonstration 42 that many non-ER organelles directly contact each other has shown that our model was wrong. 43After the ER, a second intracellular reticulum is formed by mitochondria. Although mitochondria 44 vary in size and inter-connectedness, when viewed as a whole they can form an intracellular 45 network that is almost as extensive as the ER. Like the ER, the mitochondrial network contacts 46 most other organelles. Here we review the evidence for the different contacts formed by 47 mitochondria. 48Endosome/lysosome-mitochondrion 49 contacts between endo-/lysosomes and mitochondria have been seen in several mammalian cell 50 types, where they mediate direct traffic of material. In red blood cell precursors early endosomes 51 contact mitochondria to transfer endocytosed iron for mitochondrial heme synthesis [7]. In 52 hypoxic cancer cells similar contacts allow partial "kiss and run" fusion that transfers endocytic 53 3 proteolytic enzymes to mitochondria [8]. Contact sites have also been found in pigmenting cells 54 joining melanosomes, which are lysosome-related organelles, to mitochondria, possibly for 55 production of ATP close to sites of melanization [9]. 56The best characterised contacts ...

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Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

et al. 2022

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In recent years, membrane contact sites (MCS), which mediate interactions between virtually all subcellular organelles, have been extensively characterized and shown to be essential for intracellular communication. In this review essay, we focus on an emerging topic: the regulation of MCS. Focusing on the tether proteins themselves, we discuss some of the known mechanisms which can control organelle tethering events and identify apparent common regulatory hubs, such as the VAP interface at the endoplasmic reticulum (ER). We also highlight several currently hypothetical concepts, including the idea of tether oligomerization and redox regulation playing a role in MCS formation. We identify gaps in our current understanding, such as the identity of the majority of kinases/phosphatases involved in tether modification and conclude that a holistic approach-incorporating the formation of multiple MCS, regulated by interconnected regulatory modulators-may be required to fully appreciate the true complexity of these fascinating intracellular communication systems.

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ER-to-Plasma Membrane Tethering Proteins Regulate Cell Signaling and ER Morphology

Cited by 476 publications

References 46 publications

The Arabidopsis Synaptotagmin1 Is Enriched in Endoplasmic Reticulum-Plasma Membrane Contact Sites and Confers Cellular Resistance to Mechanical Stresses

The Arabidopsis Synaptotagmin1 Is Enriched in Endoplasmic Reticulum-Plasma Membrane Contact Sites and Confers Cellular Resistance to Mechanical Stresses

Piecing Together the Patchwork of Contact Sites

Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

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