Where does the presynaptic membrane shrink

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    Membrane Neurons
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Discussion Overview

The discussion revolves around the mechanisms of membrane dynamics at the presynaptic terminal during synaptic transmission, specifically focusing on the processes that regulate the balance of membrane addition and retrieval. Participants explore the role of endocytosis and the recycling of synaptic vesicles in maintaining membrane integrity during neurotransmitter release.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant suggests that there must be a reliable process for membrane retrieval to balance the addition of membrane during neurotransmitter release, questioning what could facilitate this process.
  • Another participant references a paper indicating that ultrafast endocytosis occurs rapidly after synaptic vesicle fusion, potentially helping to maintain membrane levels during synaptic activity.
  • Questions are raised about the fate of endosomal contents and whether they could be utilized for drug delivery into neurons, with speculation on whether endosomal contents are directed to synaptic vesicles or released otherwise.
  • A later reply discusses findings from a recent study that details the transition of endocytic vesicles to endosomes and the subsequent formation of new synaptic vesicles, emphasizing the role of clathrin and actin in these processes.

Areas of Agreement / Disagreement

Participants express curiosity and propose various hypotheses regarding membrane dynamics and endocytosis, but there is no consensus on the specifics of these processes or the implications for drug delivery.

Contextual Notes

The discussion includes references to specific studies that highlight the rapid nature of endocytosis and the complexities involved in vesicle recycling, but the exact mechanisms and implications remain unresolved.

Gnomie27
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During a synapse, a synaptic vesicle fuses with the presynaptic membrane releasing whatever neurotransmitters it contains. Neurotransmitters are then taken in through transport proteins during re-uptake. Stimulation occurs on a regular basis for some neurons and since the neurotransmitters are not entering through endocytosis, the membrane would just keep building.

My thought is that there must be some reliable process that is taking in membrane just as frequently as its added to. Does anyone know what this process is? A cell probably won't just take in membrane, but bring something in with it, what could bring in so regularly?
 
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WOW! Thats incredibly, thank you!
Are the contents of an endosome ever released?
I'm just wondering if this could be used to get medicine into neurons.
Or do you think the contents go directly to synaptic vesicles?

I wonder if some HRP spread throughout the cell but was left out of the article because it was irrelevant.
If an endosome fuses with a lysosome, i guess it depends on what the lysosome does with the contents.

and what do you think stimulates this process?

Any thoughts?
 
A recent paper showed that, after fusion of synaptic vesicles with the membrane, endocytosis in the area surrounding the active zone of the presynaptic terminal occurs exremely quickly (within 50-100 ms). This ultrafast endocytosis is thought to help maintain a constant amount of membrane during synaptic activity.

See Watanabe et al. 2013. Ultrafast endocytosis at mouse hippocampal synapses. Nature 504: 242. http://dx.doi.org/10.1038/nature12809 .
 
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Gnomie27 said:
WOW! Thats incredibly, thank you!
Are the contents of an endosome ever released?
I'm just wondering if this could be used to get medicine into neurons.
Or do you think the contents go directly to synaptic vesicles?

The same group that published the study about ultrafast endocytosis that I cited above just published a new paper in Nature. Here, they look at the fate of the endocytic vesicles after ultrafast endocytosis, which shows they traffic to endosomes, and new synaptic vesicles bud from these endosomes. Here's the abstract from the study:
Ultrafast endocytosis can retrieve a single, large endocytic vesicle as fast as 50–100 ms after synaptic vesicle fusion. However, the fate of the large endocytic vesicles is not known. Here we demonstrate that these vesicles transition to a synaptic endosome about one second after stimulation. The endosome is resolved into coated vesicles after 3 s, which in turn become small-diameter synaptic vesicles 5–6 s after stimulation. We disrupted clathrin function using RNA interference (RNAi) and found that clathrin is not required for ultrafast endocytosis but is required to generate synaptic vesicles from the endosome. Ultrafast endocytosis fails when actin polymerization is disrupted, or when neurons are stimulated at room temperature instead of physiological temperature. In the absence of ultrafast endocytosis, synaptic vesicles are retrieved directly from the plasma membrane by clathrin-mediated endocytosis. These results may explain discrepancies among published experiments concerning the role of clathrin in synaptic vesicle endocytosis.

Watanabe et al. 2014. Clathrin regenerates synaptic vesicles from endosomes. Nature. 525: 228. http://dx.doi.org/10.1038/nature13846
 
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