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ER Organization in Neuronal Polarity
Ginny G. Farías 1
1 Cell Biology, Neurobiology and Biophysics, Department of Biology, Utrecht University, The Netherlands
Establishment of neuronal polarity depends on local microtubule (MT) reorganization and organelle dynamics. The
endoplasmic reticulum (ER) consists of cisternae and tubules and, like MTs, forms an extensive network throughout
the entire cell. How the two networks interact and control neuronal development is an outstanding question. We
found that the interplay between MTs and ER tubules is essential for neuronal polarity. MTs are essential for axonal
ER tubule stabilization, and reciprocally, ER tubules are required for stabilizing and organizing axonal MTs.
Recruitment of ER tubules into one minor neurite initiates axon formation, whereas local ER tubule disruption
prevent neuronal polarization.
In addition to ER – MT interactions, the ER forms contact with other organelles. How this interaction
contributes to the organization, dynamics and polarized distribution of other organelles in neurons remains unclear.
We found that local somatic ER tubules contribute to the axonal distribution of lysosomes. Somatic ER tubule
disruption causes enlarged lysosomes accumulated in the soma, preventing their entrance to the axon. We identified
a somatic ER tubule array, enriched at a pre-axonal region, which ensures co-stabilization of ER tubule – MT –
lysosome contacts to promote kinesin-1-driven lysosome fission and their translocation into the axon.
Lastly, ER cisternae, involved in translation of transmembrane and secretion proteins are absent along the
axon. Unexpectedly, we found axonal ER tubule in contact with ribosomes in developing neurons. This interaction
is regulated by neuronal stimuli and is required for proper local axonal translation. Disruption of ER tubule –
ribosome contact impairs axonal translation.
Thus, neuronal ER tubule plays an essential role in maintaining axonal identity, by organizing MTs, and
regulating both axonal lysosome availability and local axonal translation.
[This work has been supported by European Research Council (ERC‐StG 950617) to GGF; Netherlands Organization of
Scientific Research (0.16.VIDI.189.019) to GGF; Netherlands Organization of Scientific Research (VI.VENI.202.113) to MK]