Related Experiment Video
Updated: Feb 12, 2026
08:59
Defining Substrate Specificities for Lipase and Phospholipase Candidates
Published on: November 23, 2016
15.6K
The phospholipase A2 pathway controls a synaptic cholesterol ester cycle and synapse damage
Craig Osborne1, Ewan West1, Clive Bate2
1Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, UK AL9 7TA.
Journal of Cell Science
|March 29, 2018
Summary
Platelet activating factor (PAF) regulates cholesterol metabolism and signaling complex formation in synapses. This process influences synapse degeneration by controlling cytoplasmic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2) activation.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Cellular prion protein (PrPC) organizes signaling complexes in synaptosomes.
- Amyloid-β (Aβ) oligomers aggregate PrPC, activating cytoplasmic phospholipase A2 (cPLA2) and leading to synapse degeneration.
- Synaptic signaling platforms rely on cholesterol released by cholesterol ester hydrolases (CEHs).
Purpose of the Study:
- To investigate the role of platelet activating factor (PAF) in regulating synaptic signaling complexes.
- To elucidate the mechanisms of signaling complex dispersal and cessation of signaling.
- To understand the involvement of cholesterol esterification in synapse protection.
Main Methods:
- Investigated the formation and dispersal of Aβ-PrPC-cPLA2 signaling complexes.
- Examined the role of PAF in the recruitment of Fyn and COX-2.
- Studied the effect of acyl-coenzyme A:cholesterol acyltransferase (ACAT)-1 on cholesterol levels and complex stability.
Main Results:
- A positive feedback loop exists where activated cPLA2 increases cholesterol, further activating cPLA2.
- PAF is crucial for incorporating Fyn and COX-2 into signaling complexes.
- PAF-mediated recruitment of ACAT-1 esterifies cholesterol, dispersing complexes and halting signaling.
Conclusions:
- PAF is a key regulator of the cholesterol ester cycle, cPLA2, and COX-2 activation in synapses.
- Cholesterol esterification by ACAT-1 is essential for dispersing signaling complexes and preventing synapse damage.
- Understanding these mechanisms offers insights into synapse degeneration and potential therapeutic targets.
Related Concept Videos
02:47The Synapse
133.7K
Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
133.7K
01:12Synaptic Signaling
79.8K
Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
79.8K
02:36DNA Damage Can Stall the Cell Cycle
3.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.2K
02:36DNA Damage can Stall the Cell Cycle
10.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.2K
01:28The Cell Cycle Control System
5.7K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
5.7K
02:11The Cell Cycle Control System
14.5K
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
14.5K