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Cited by 242Gastrointestinal motility and disordersIon Channels and ReceptorsNeuroscience and Neuropharmacology Research

An Enteroendocrine Cell – Enteric Glia Connection Revealed by 3D Electron Microscopy

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Bohórquez, Diego V., Samsa, Leigh A., Roholt, Andrew, Medicetty, Satish, Chandra, Rashmi, Liddle, Rodger A.·2014·PLoS ONE
DOI 10.1371/journal.pone.0089881PMC PMC3935946
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Abstract

The enteroendocrine cell is the cornerstone of gastrointestinal chemosensation. In the intestine and colon, this cell is stimulated by nutrients, tastants that elicit the perception of flavor, and bacterial by-products; and in response, the cell secretes hormones like cholecystokinin and peptide YY--both potent regulators of appetite. The development of transgenic mice with enteroendocrine cells expressing green fluorescent protein has allowed for the elucidation of the apical nutrient sensing mechanisms of the cell. However, the basal secretory aspects of the enteroendocrine cell remain largely unexplored, particularly because a complete account of the enteroendocrine cell ultrastructure does not exist. Today, the fine ultrastructure of a specific cell can be revealed in the third dimension thanks to the invention of serial block face scanning electron microscopy (SBEM). Here, we bridged confocal microscopy with SBEM to identify the enteroendocrine cell of the mouse and study its ultrastructure in the third dimension. The results demonstrated that 73.5% of the peptide-secreting vesicles in the enteroendocrine cell are contained within an axon-like basal process. We called this process a neuropod. This neuropod contains neurofilaments, which are typical structural proteins of axons. Surprisingly, the SBEM data also demonstrated that the enteroendocrine cell neuropod is escorted by enteric glia--the cells that nurture enteric neurons. We extended these structural findings into an in vitro intestinal organoid system, in which the addition of glial derived neurotrophic factors enhanced the development of neuropods in enteroendocrine cells. These findings open a new avenue of exploration in gastrointestinal chemosensation by unveiling an unforeseen physical relationship between enteric glia and enteroendocrine cells.

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Crossref · 10.1371/journal.pone.0089881

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  • A basolateral cytoplasmic process of L cells, the neuropod, establishes a functional synaptic contact with enteric glia and vagal afferents.

    “A basolateral cytoplasmic process of the L cells -the neuropod -was shown to establish a functional synaptic contact with the enteric glia and vagal afferents.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Bohorquez et al., 2014

    The Results section ('3D Ultrastructure Reveals Axonal Process Escorted by Enteric Glia'; page unavailable) shows that an enteric glial process contacts an enteroendocrine-cell neuropod. It also says there was no evident structural specialization at the contact point. The copy does not establish a functional synapse with glia or show contact with vagal afferents. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Bohórquez, D. V., Samsa, L. A., Roholt, A., Medicetty, S., Chandra, R., & Liddle, R. A.
Affiliations
  • Duke Medical Center (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Bohórquez, Diego V.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-02-26
Volume
9
Issue
2
Pages
e89881
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0089881
PMC
PMC3935946
OpenAlex
W2069081742
Cited by
242
References
8
Citations by year
2026: 18 · 2025: 17 · 2024: 21 · 2023: 25 · 2022: 22 · 2021: 26 · 2020: 15 · 2019: 17 · 2018: 22 · 2017: 16 · 2016: 21 · 2015: 18 · 2014: 4
FWCI
18.36
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
  • Figshare (submittedVersion, cc-by)
  • UNC Libraries
Funders
  • U.S. Department of Veterans Affairs (I01 BX002230)
  • North Carolina State University
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (T32HL069768)
  • National Cancer Institute (P30CA014236)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F32DK094704, DK098796, R01DK098796, R01DK091946)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
enteroendocrine cells, enteric glial cells, neurofilaments, glial cell line-derived neurotrophic factor, intestinal organoids, cholecystokinin, peptide YY, appetite regulation, enteric nervous system
MeSH terms
Animals, Intermediate Filaments, Microscopy, Electron, Scanning, Microscopy, Confocal, Enteroendocrine Cells, Imaging, Three-Dimensional, Cell Surface Extensions, Secretory Vesicles, Mice

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