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An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy.
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.
Type
Journal articleSubject
AnimalsCell Surface Extensions
Enteroendocrine Cells
Imaging, Three-Dimensional
Intermediate Filaments
Mice
Microscopy, Confocal
Microscopy, Electron, Scanning
Secretory Vesicles
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https://hdl.handle.net/10161/9382Published Version (Please cite this version)
10.1371/journal.pone.0089881Publication Info
Bohórquez, Diego V; Samsa, Leigh A; Roholt, Andrew; Medicetty, Satish; Chandra, Rashmi;
& Liddle, Rodger A (2014). An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy.
PLoS One, 9(2). pp. e89881. 10.1371/journal.pone.0089881. Retrieved from https://hdl.handle.net/10161/9382.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Diego V. Bohorquez
Associate Professor in Medicine
I am a gut-brain neuroscientist. Though my initial studies focused on GI physiology
and nutrition, my expertise evolved to include neuroscience following the many personal
stories, which have carefully sharpened my career vision along the way. While pursuing
a Doctoral degree in Nutrition, a friend shared her struggles with obesity and gastric
bypass surgery. Surgery was a last resort but helped to reduced her body weight dramatically
and resolved her diabe
Rodger Alan Liddle
Professor of Medicine
Our laboratory has two major research interests:Enteroendocrine Cell Biology
Enteroendocrine cells (EECs) are sensory cells of the gut that send signals throughout
the body. They have the ability to sense food and nutrients in the lumen of the intestine
and secrete hormones into the blood. Our laboratory has had a longstanding interest
in two types of EECs that regulate satiety and signal the brain to stop eating. Chole
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