It comes as a fact in most works that polypeptides can escape vesicles and interact with proteasomes/cytoplasmic proteins/etc.. However, the mechanism of such endosomal release is not obvious and as long as I know has not been studied well. I would be happy to receive any information concerning mechanisms of endosomal escape.
Thank you!
It's not brief, nor is it a complete answer, but a few years back a colleague and I summarized the literature on proteins that were found in these topologically distinct compartments, with a particular focus on nuclear proteins also found in extracellular domains.
Article Dual localization: Proteins in extracellular and intracellul...
Hi,
It depends on the peptides. In case of some peptides it is possible that they self-assemble and are taken up as aggregates/nanoparticles, which might change their uptake/release mechanisms also. So you might want to look into particle uptake/release papers also. Here is one nice paper on endosomal release of siRNA lipoplexes: http://www.nature.com/nbt/journal/v33/n8/full/nbt.3298.html
Good luck!
Dear Eevengy,
In relation to your question, I can say that recycling back to membrane or scape of degradation are not aleatory phenomena, but biochemical regulated process. Hence, its depends on the instantaneous state of the biochemcial species involved. For example, in the case of ionotropic receptors (NMDAR and AMPAR), to be endocyted is required some modifications in the cytoskeleton while simultaneously must be activated Fyn*, CDK5*, AP2 proteins. Instead, to be recycled must be activated proteins RAB11 and NSF. In turn, proteasome has its own, complex regulation, mainly at the pre-processing of the proteins by E1, E2, and E3 Ubiquitin ligase systems. I hope you find some orientation in this information, but you have analyse the regulation of your specific proteins. Best
Daniel
Tõnis, thank you for the most appropriate answer to my question. Actually, siRNA release you have mentioned is the only mechanism of endosomal escape being deeply described. I will look into it.
Dmitri, I can try, though the question mainly concerns absence of references about endosomal escape of beta-amyloid peptide.
LaFerla et al. 2007 review in Nature Reviews/Neuroscience discusses well-known effects of cytoplasmic Abeta (proteasome interaction, tau hyperphosphorylation, mitochondria function impairment) and nothing is said about HOW vesicular amyloid enters cytoplasm.
Particularly, in article Oh, Hong, 2005, devoted to proteasome inhibition by beta-amyloid, authors show cytoplasmic localisation of Abeta peptide after treatment of cells with extracellular synthetic amyloid, which also requires a mechanism of endosomal release.
I am not sure if the answer is still relevant,
I have used a polypeptide in my study to check the mechanism of ZnO nanowires for penetration and endocytosis:
https://www.researchgate.net/publication/319647058_Efficient_intracellular_delivery_of_biomacromolecules_employing_clusters_of_zinc_oxide_nanowires
Although this one is not the cell penetrating peptide but still can help in understanding the problem.
I used DNA tagged with peptide which integrated with Cellular DNA and expressed, but the most of the DNA tagged peptide are endocytosed and degraded.
The concentration and penetration efficiency direct the peptide to different cell organelles can be one of the reasons.
I am not sure if my paper can throw some light on it.
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