Cholesterol, regulated exocytosis and the physiological fusion machine.

@article{Churchward2009CholesterolRE,
  title={Cholesterol, regulated exocytosis and the physiological fusion machine.},
  author={Matthew A Churchward and Jens R Coorssen},
  journal={The Biochemical journal},
  year={2009},
  volume={423 1},
  pages={
          1-14
        }
}
Exocytosis is a highly conserved and essential process. Although numerous proteins are involved throughout the exocytotic process, the defining membrane fusion step appears to occur through a lipid-dominated mechanism. Here we review and integrate the current literature on protein and lipid roles in exocytosis, with emphasis on the multiple roles of cholesterol in exocytosis and membrane fusion, in an effort to promote a more molecular systems-level view of the as yet poorly understood process… 
View on PubMed
biochemj.org
60 Citations
Highly Influential Citations
7
Background Citations
22
Methods Citations
1
Results Citations
1

Figures and Tables from this paper

60 Citations

Lipid Dynamics in Exocytosis

The latest advances in this rapidly developing field revealing that lipids actually play an active role in exocytosis by focusing on cholesterol, 3′-phosphorylated phosphoinositides and phosphatidic acid are presented.

Cholesterol and regulated exocytosis: a requirement for unitary exocytotic events.

Critical Role of Cortical Vesicles in Dissecting Regulated Exocytosis: Overview of Insights Into Fundamental Molecular Mechanisms

The establishment of sea urchin cortical vesicle fusion is discussed as a model to study regulated exocytosis—a system in which the docked, release-ready, and late Ca2+-triggered steps of exocyTosis are isolated and can be quantitatively assessed using the rigorous coupling of functional and molecular assays.

Lipid–protein interactions in exocytotic release of hormones and neurotransmitters

The importance of specific lipids and lipid–protein interactions in regulated release of neurotransmitters and hormones is highlighted, as they appear to be critical for regulating the entire process of exocytosis.

High cholesterol obviates a prolonged hemifusion intermediate in fast SNARE-mediated membrane fusion.

Exocytotic fusion pore under stress

Post-fusion mechanisms that regulate fusion pore stability are considered, reflecting the state in which the forces of widening and constriction of fusion pores are balanced.

How to Make a Stable Exocytotic Fusion Pore, Incompetent of Neurotransmitter and Hormone Release from the Vesicle Lumen?

Exocytotic fusion pores as a target for therapy.

Fusion pore regulation in peptidergic vesicles.

Application of High-Throughput Assays to Examine Phospho-Modulation of the Late Steps of Regulated Exocytosis

Results indicate the presence of multiple kinases and phosphatases on the vesicles and critical phosphorylation sites on vesicle membrane proteins and lipids that directly influence late steps of regulated exocytosis.
...

References

SHOWING 1-10 OF 258 REFERENCES

Control of fusion pore dynamics during exocytosis by Munc18.

A Munc18 mutant with reduced affinity for syntaxin is expressed in adrenal chromaffin cells, which specifically modified the kinetics of single-granule exocytotic release events, consistent with an acceleration of fusion pore expansion.

Phospholipase D in calcium-regulated exocytosis: lessons from chromaffin cells.

How can proteolipids be central players in membrane fusion?

Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis

The fusion pore of regulated exocytosis is a channel that connects and spans the vesicle and plasma membranes. The molecular composition of this important intermediate structure of exocytosis is…

The multiple faces of caveolae

The apparently diverse functions of caveolae, including mechanosensing and lipid regulation, might be linked to their ability to respond to plasma membrane changes, a property that is dependent on their specialized lipid composition and biophysical properties.

Synaptic vesicle fusion

The core of the neurotransmitter release machinery is formed by SNARE complexes, which bring the vesicle and plasma membranes together and are key for fusion, and by Munc18-1, which controls…

Revisiting the role of SNAREs in exocytosis and membrane fusion.

The role of transmembrane domains in membrane fusion

Although both types of fusion proteins are evolutionarily quite distant from each other, they do share a number of structural and functional features, and their transmembrane domains are now known to be critical for the fusion reaction.

Comment on "Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis"

A model in which multiple syntaxin transmembrane domains (TMDs) act as subunits of a proteinaceous fusion pore is described, which seems intriguing.

Lysophosphatidylcholine reversibly arrests exocytosis and viral fusion at a stage between triggering and membrane merger.

...