scholarly journals Lipid Transfer Proteins and Membrane Contact Sites in Human Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Diego Peretti ◽  
SoHui Kim ◽  
Roberta Tufi ◽  
Sima Lev
Keyword(s):  
Human Cancer ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

scholarly journals The Hob Proteins: Putative, Novel Lipid Transfer Proteins at ER-PM Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110523
Author(s):  
Sarah D. Neuman ◽  
Amy T. Cavanagh ◽  
Arash Bashirullah
Keyword(s):  
Structural Models ◽  
Model Systems ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Bona Fide ◽  
Membrane Contact ◽  
Mutant Cells ◽  
Critical Process

Nonvesicular transfer of lipids at membrane contact sites (MCS) has recently emerged as a critical process for cellular function. Lipid transfer proteins (LTPs) mediate this unique transport mechanism, and although several LTPs are known, the cellular complement of these proteins continues to expand. Our recent work has revealed the highly conserved but poorly characterized Hobbit/Hob proteins as novel, putative LTPs at endoplasmic reticulum-plasma membrane (ER-PM) contact sites. Using both S. cerevisiae and D. melanogaster model systems, we demonstrated that the Hob proteins localize to ER-PM contact sites via an N-terminal ER membrane anchor and conserved C-terminal sequences. These conserved C-terminal sequences bind to phosphoinositides (PIPs), and the distribution of PIPs is disrupted in hobbit mutant cells. Recently released structural models of the Hob proteins exhibit remarkable similarity to other bona fide LTPs, like VPS13A and ATG2, that function at MCS. Hobbit is required for viability in Drosophila, suggesting that the Hob proteins are essential genes that may mediate lipid transfer at MCS.

scholarly journals Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing?

2016 ◽  
Vol 44 (2) ◽  
pp. 517-527 ◽  
Author(s):  
Louise H. Wong ◽  
Tim P. Levine
Keyword(s):  
Lipid Binding ◽  
Lipid Transfer ◽  
Transmembrane Helices ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Multiple Contacts ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Lipid Binding Proteins

Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices so that they cannot diffuse through the cytosol to deliver lipids. If such proteins target membrane contact sites they may be major players in lipid metabolism. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices anchoring them in the endoplasmic reticulum (ER), making them interesting subjects for study in relation to sterol metabolism. They target a variety of membrane contact sites, including newly described contacts between organelles that were already known to make contact by other means. Lam1–4p target punctate ER–plasma membrane contacts. Lam5p and Lam6p target multiple contacts including a new category: vacuolar non-NVJ cytoplasmic ER (VancE) contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that established the importance of membrane anchored proteins for lipid traffic. However, the question remaining to be solved is the most difficult of all: are LAMs transporters, or alternately are they regulators that affect traffic more indirectly?

ER-Golgi membrane contact sites

2020 ◽  
Vol 48 (1) ◽  
pp. 187-197 ◽  
Author(s):  
Rossella Venditti ◽  
Maria Chiara Masone ◽  
Maria Antonietta De Matteis
Keyword(s):  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Lipid Exchange ◽  
Pathological Conditions ◽  
The Sixties ◽  
In Trans ◽  
Membrane Contact ◽  
Methodological Approaches

Membrane contact sites (MCSs) are sites where the membranes of two different organelles come into close apposition (10–30 nm). Different classes of proteins populate MCSs including factors that act as tethers between the two membranes, proteins that use the MCSs for their function (mainly lipid or ion exchange), and regulatory proteins and enzymes that can act in trans across the MCSs. The ER-Golgi MCSs were visualized by electron microscopists early in the sixties but have remained elusive for decades due to a lack of suitable methodological approaches. Here we report recent progress in the study of this class of MCSs that has led to the identification of their main morphological features and of some of their components and roles. Among these, lipid transfer proteins and lipid exchange have been the most studied and understood so far. However, many unknowns remain regarding their regulation and their role in controlling key TGN functions such as sorting and trafficking as well as their relevance in physiological and pathological conditions.

scholarly journals SNAP iN, SNAP oUT—SNAREs at ER-PM Contact Sites

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642097958
Author(s):  
Neha Pratap Singh ◽  
Christian Vannier ◽  
Thierry Galli
Keyword(s):  
Protein Complexes ◽  
Short Review ◽  
Lipid Transfer ◽  
Contact Site ◽  
Lipid Transfer Proteins ◽  
Homologous Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Organelle Communication

Inter-organelle communication is essential for the exchange of cellular content in eukaryotes, particularly at membrane contact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM). Accomplishing this critical task requires close positioning of the involved membranes via tether proteins and associated complexes. One such complex involves the SNAREs Sec22b and Syntaxin 1. Discovered to be interacting at the ER-PM membrane contact site (MCS), Sec22b-Stx1 forms a unique non-fusogenic bridge tethering the two membranes. Contrarily, SNAP25 was shown to be absent from the Sec22b-Stx1 complexes. Two recent studies focused on this interplay of SNARES and Lipid transfer proteins at MCSs. The Longin domain of Sec22b appeared to be the reason behind SNAP25’s exclusion from Sec22b-Stx1 assembly, and inclusion of E-Syts. It was also shown that yeast Sec9p and mammalian SNAP25 regulate ER-PM contact sites via their interaction with LTP OSBP-homologous proteins (ORP/OSH). In this following short review, we will take a closer look at the protein complexes involving SNAREs at MCSs and potential regulation by the Longin domain of Sec22b.

scholarly journals ORP5 AND ORP8 ORCHESTRATE LIPID DROPLET BIOGENESIS AND MAINTENANCE AT ER-MITOCHONDRIA CONTACT SITES

2021 ◽  
Author(s):  
Valentin Guyard ◽  
Vera F Monteiro-Cardoso ◽  
Mohyeddine Omrane ◽  
Cecile Sauvanet ◽  
Audrey Houcine ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Phosphatidic Acid ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Nucleation And Growth ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Lipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the Endoplasmic Reticulum (ER). The ER-protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at Mitochondria-Associated ER Membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulate seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for the ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at membrane contact sites.

Non-vesicular lipid trafficking at the endoplasmic reticulum–mitochondria interface

2018 ◽  
Vol 46 (2) ◽  
pp. 437-452 ◽  
Author(s):  
Francesca Giordano
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transport Pathways ◽  
Lipid Trafficking ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Mitochondria are highly dynamic organelles involved in various cellular processes such as energy production, regulation of calcium homeostasis, lipid trafficking, and apoptosis. To fulfill all these functions and preserve their morphology and dynamic behavior, mitochondria need to maintain a defined protein and lipid composition in both their membranes. The maintenance of mitochondrial membrane identity requires a selective and regulated transport of specific lipids from/to the endoplasmic reticulum (ER) and across the mitochondria outer and inner membranes. Since they are not integrated in the classical vesicular trafficking routes, mitochondria exchange lipids with the ER at sites of close apposition called membrane contact sites. Deregulation of such transport activities results in several pathologies including cancer and neurodegenerative disorders. However, we are just starting to understand the function of ER–mitochondria contact sites in lipid transport, what are the proteins involved and how they are regulated. In this review, we summarize recent insights into lipid transport pathways at the ER–mitochondria interface and discuss the implication of recently identified lipid transfer proteins in these processes.

Sign in / Sign up

Export Citation Format

Share Document