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Cited by 32Cellular transport and secretionIon Channels and ReceptorsEndoplasmic Reticulum Stress and Disease

The ER ladder is a unique morphological feature of developing mammalian axons

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Zamponi, Emiliano, Meehl, Janet B., Voeltz, Gia K.·2022·Developmental Cell
DOI 10.1016/j.devcel.2022.05.002
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Abstract

The endoplasmic reticulum (ER) confronts a challenge to accommodate long, smooth ER tubules into the structural complexity of the axonal compartment. Here, we describe a morphological feature for the axonal ER network in developing neurons we termed the ER ladder. Axonal ER ladders are composed of rungs that wrap tightly around the microtubule bundle and dynamic rails, which slide across microtubules. We found that the ER-shaping protein Reticulon 2 determines the architecture and dynamics of the axonal ER ladder by modulating its interaction with microtubules. Moreover, we show that ER ladder depletion impairs the trafficking of associated vesicular axonal cargoes. Finally, we demonstrate that stromal interaction molecule 1 (Stim1) localizes to ER rungs and translocates to ER-plasma membrane contact sites upon depletion of luminal Ca 2+ . Our findings uncover fundamental insights into the structural and functional organization of the axonal ER network in developing mammalian neurons.

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  • Several studies have imaged neuronal processes by cryo-EM and cryo-ET, showing neurites are accessible to cryogenic imaging but persistent challenges remain at molecular resolution due to poor contrast and cytoplasmic denseness.

    “Several studies have imaged neuronal processes by cryo-EM and cryo-ET19–25, showing that neurites are accessible to cryogenic imaging, while also revealing persistent challenges in obtaining information at a molecular resolution due to poor contrast and cytoplasmic denseness.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [24]

    The Results (page unavailable) describe cryo-ET imaging of developing axons and visualization of their structures at nanometer resolution, supporting the claim that neuronal processes are accessible to cryogenic imaging. The paper does not attribute difficulty obtaining molecular-resolution information to poor contrast or cytoplasmic denseness; its comment about poor resolution concerns conventional TEM instead. (LLM, conf=0.84)

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Authors
Zamponi, E., Meehl, J. B., & Voeltz, G. K.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Voeltz, Gia K.
ORCID
Voeltz, Gia K.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2022-06
Volume
57
Issue
11
Pages
1369-1382.e6
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2022.05.002
OpenAlex
W4281286433
Cited by
32
References
2
Citations by year
2026: 7 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 1
FWCI
3.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Howard Hughes Medical Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
microtubule interaction, ER dynamics, vesicle trafficking, STIM1, ER-plasma membrane contact sites, calcium signaling, developing neurons, axon development
MeSH terms
Animals, Axons, Calcium, Cytoskeleton, Endoplasmic Reticulum, Mammals, Microtubules, Neurons

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