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Congrats, looking forward to what you'll uncover!

Awesome, congrats!!:)

This seem to be two separate issues. Tool used vs quality of outcome. I'm sure there were lazy submissions before LLMs - how were those handled?

Plants have many complementing MCTP homologs (the reticulon-containing proteins likely shaping desmotubules) so mutants are difficult. Animals only have 2 copies, one of which localizes to axonal ER: elifesciences.org/articles/22904

MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticityMCTP is a novel presynaptic calcium sensor, resident within the endoplasmic reticulum, that is required for normal baseline neurotransmission, short-term synaptic plasticity and presynaptic homeostati...elifesciences.org

Thank you so much, also to the PD community as a whole, for the warm welcome.

Thanks a lot!😁

desmotubule is 10nm outer diameter, so barely any lumen after subtracting membranes

Fig.2 here nicely illustrates the cell wall formation (PM in magenta) around the ER (green) in the center of a dividing cell. www.science.org/doi/10.1126/...

Plant plasmodesmata bridges form through ER-dependent incomplete cytokinesisDiverging from conventional cell division models, plant cells undergo incomplete division to generate plasmodesmata communication bridges between daughter cells. Although fundamental for plant multice...www.science.org

Thanks for the paper! So axon ER is 3x wider than desmotubules and has mobile lumen. As to why ER-as-scaffold in PD: it is inherited developmentaly. ER is trapped in forming cell walls during cytokinesis, later becoming the desmotubule in PD of the mature wall used to organize PD protein machinery.

Thanks Ralf! Physco turned out to be a good cryoET system:)

In that model making it narrow could be advantageous - maximizing the surrounding transport space. Don't know about axons but could it also be to organize signaling machinery?

Thanks Cahir and great point! As far as we know the desmotubule is more of a scaffold than a pipe. It stabilizes PD during cell division and organizes protein machinery like the coatings resolved here. The main route is thought to be the cytosol-filled sleeve between it and the PM.

Thanks a lot JC!

Thanks a lot Kasper!

Regarding calreticulin, we do observe small protein densities clustering in the ER lumen near PD apertures but these features are too small and irregular to assign to specific proteins currently.

it gets crowded within the pores and we cannot exclude non-filamentous, low-copy, and/or transient actin in the cytosolic sleeve.

Great question, thanks! F-actin is easy to spot in tomograms and we do not see it at PD. We also tested whether actin could account for the desmotubule coat, but it does not fit the resolved geometry whereas MCTPs are a very good fit. That said, ...

Thank you Mary!:)

Thank you Alexej!!:)

My blind guess is TFs need disordered parts to sample DNA efficiently. You could try predict in presence of the corresponding DNA motif using AF3 and see if that produces more secondary structure