Endosome Puns

I'm a capsid biologist. I have HIV-1 trafficking on my mind more often than I'd like to admit. Can't be bothered to be properly icosahedral, might be uncoating in the nucleus... it's all screwed up.

Last I heard, and the tide is changing constantly, SARS-CoV-2 could use a direct fusion pathway or be endocytosed for entry. In the latter case it's moving within a vesicle along microtubules, and that makes perfect sense.

But if the SARS-CoV-2 particle does directly fuse and just dumps a helical RNA-NC complex within the cytoplasm........... how does that complex accomplish any movement away from the cell periphery?

Edit to add: The latest data I’ve read don’t implicate microtubules at all in SARS-CoV-2 dsRNA localization, and instead show some weird dependence on intermediate filaments. So I don’t think NC here is substituting for CA in some kind of motor interaction.

what are they and what's the difference ?

I'm a bit confused by a question from a third party qbank. It talks about the endosomal pathway, and then alternative pathways, but I'm unclear if late endsome is shuttled to lysosome for degradation or it turns into a lysosome.

Thanks in advance

Unidirectional penetration along minimalist pH gradients is developed as a strategy to label the membrane of early endosomes with mechanosensitive flipper probes, by simple addition to unmodified cells. Substituted benzylamines offer the right acidity, pKa=10, not too strong to allow reversibility, not too weak to inhibit penetration from neutral water in the cytosol, and, perhaps, extra returns from interfacial aromatic anchoring.

Abstract

Fluorescent flipper probes have been introduced recently to image membrane tension in live cells, and strategies to target these probes to specific membranes are emerging. In this context, early endosome (EE) targeting without the use of protein engineering is especially appealing because it translates into a fascinating transport problem. Weakly basic probes, commonly used to track the inside of acidic late endosomes and lysosomes, are poorly retained in EE because they are sufficiently neutralized in weakly acidic EE, thus able to diffuse out. Here, we disclose a rational strategy to target EE using a substituted benzylamine with a higher pKa value as a head group of the flipper probe. The resulting EE flippers are validated for preserved mechanosensitivity, ready for use in biology, particularly to elucidate the mechanics of endocytosis.

https://ift.tt/3xyKaSb

Hey guys, so none of my textbooks seem to explain this comprehensively and I'm really confused on what exactly these do, along with the Golgi. This is what I have so far:

Endosomes:

- Carbohydrates, proteins, and lipids (is this accurate?) get transported from the rough (proteins) and smooth (lipids, dunno where carbohydrates come from) ER's to the cis-Golgi, then get shipped out in vesicles from the trans-Golgi.

- From there, they go to either 1) cell membrane 2) parts of the cell or 3) lysosomes.

Lysosomes:

- Degrade stuff via hydrolytic enzymes.

- Can lyse to release their enzyme contents, triggering apoptosis of the cell.

- Can degrade phagocytosed pathogens via phagolysosomes.

Where I'm getting confused is:

1) Are there additional functions of endosomes or lysosomes that're not written here that we should know at a bio 101 level?

2) So I get that lysosomes can degrade stuff, but what is the purpose of it? Like what happens to the degraded stuff once it's broken down in the lysosome? Is it recycled/excreted?

3) A question said that a cell phagocytoses a carbohydrate, which gets digested in the lysosome. So does that mean things can go to the lysosomes via 2 pathways:

- Endocytosis > endosome > lysosome (ie starting from outside the cell) or
- ER > Golgi > endosome > lysosome (ie starting from inside the cell)?

4) What are lysosomes able and not able to degrade?

Thank you!

Fluorescent flipper probes have been introduced recently to image membrane tension in live cells, and strategies to target these probes to specific membranes are emerging.   In this context, early endosomes (EE) targeting without use of protein engineering is especially appealing because it translates into a fascinating transport problem.   Weakly basic probes, commonly used to track inside acidic late endosomes and lysosomes, are poorly retained in EE because they are sufficiently neutralized in weakly acidic EE, thus able to diffuse out.   Here, we disclose a rational strategy to target EE using a substituted benzylamine with higher pK a as a head group of the flipper probe.   The resulting EE flippers are validated for preserved mechanosensitivity, ready for use in biology, particularly to elucidate the mechanics of endocytosis.

https://ift.tt/3jrr7m9