Lysophosphatidylcholine inhibits membrane-associated SNARE complex disassembly
Leah Shin1, Sunxi Wang, Jin-Sook Lee
1Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
Journal of Cellular and Molecular Medicine
|September 3, 2011
Summary
Membrane lipids like cholesterol and L-α-lysophosphatidylcholine (LPC) impact SNARE complex disassembly. LPC inhibits disassembly, potentially affecting membrane fusion and protein secretion in cancer.
Area of Science:
- Cell biology
- Neuroscience
- Biochemistry
Background:
- N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors (SNAREs) mediate membrane fusion, crucial for processes like neurotransmission.
- Lipids, including cholesterol and L-α-lysophosphatidylcholine (LPC), influence membrane curvature and dynamics.
- Dysregulated SNARE function is implicated in various cellular processes and diseases.
Purpose of the Study:
- To investigate the role of membrane-curvature-influencing lipids on SNARE complex disassembly.
- To determine how cholesterol and LPC affect the NSF-mediated disassembly of neuronal SNARE complexes.
- To explore the potential implications of these findings in the context of cancer.
Main Methods:
- Utilized purified recombinant neuronal SNAREs reconstituted into liposomes.
- Assessed SNARE complex disassembly in liposome mixtures containing cholesterol or LPC upon exposure to NSF-ATP.
- Examined the effects of cholesterol and LPC on SNARE complex disassembly in isolated rat brain slices and pancreas.
Main Results:
- Cholesterol-associated SNARE liposomes showed NSF-ATP-induced vesicle dissociation.
- LPC-associated SNARE liposomes exhibited inhibited SNARE complex disassembly and vesicle clustering upon NSF-ATP exposure.
- In vivo experiments with rat brain slices and pancreas confirmed LPC-induced inhibition of SNARE complex disassembly.
Conclusions:
- Membrane lipids, particularly LPC, profoundly influence SNARE complex disassembly dynamics.
- LPC-induced inhibition of SNARE disassembly may contribute to altered membrane fusion and protein secretion observed in cancers with elevated LPC levels.
- These findings highlight a novel lipid-mediated regulatory mechanism for membrane fusion machinery.
More Related Videos
10:58SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy
Published on: August 24, 2016
07:33Lipid Vesicle-mediated Affinity Chromatography using Magnetic Activated Cell Sorting (LIMACS): a Novel Method to Analyze Protein-lipid Interaction
Published on: April 26, 2011
Related Concept Videos
01:27Synthesis of Phosphatidylcholine in the ER Membrane
The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
The major components of all eukaryotic cell...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:43SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:28Depolarizing Blockers: Mechanism of Action
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because succinylcholine...
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...