Clathrin heavy chain 22 contributes to the control of neuropeptide degradation and secretion during neuronal development.
Authors
Nahorski, Michael Stefan
Shaikh, Samiha S
Al-Gazali, Lihadh
Antrobus, Robin
Woods, Geoff
Publication Date
2018-02-05Journal Title
Scientific reports
ISSN
2045-2322
Publisher
Nature Publishing Group
Volume
8
Issue
1
Pages
2340
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Nahorski, M. S., Borner, G. H., Shaikh, S. S., Davies, A., Al-Gazali, L., Antrobus, R., & Woods, G. (2018). Clathrin heavy chain 22 contributes to the control of neuropeptide degradation and secretion during neuronal development.. Scientific reports, 8 (1), 2340. https://doi.org/10.1038/s41598-018-19980-0
Abstract
The repertoire of cell types in the human nervous system arises through a highly orchestrated
process, the complexity of which is still being discovered. Here, we present evidence that
CHC22 has a non-redundant role in an early stage of neural precursor differentiation,
providing a potential explanation of why CHC22 deficient patients are unable to feel touch or
pain. We show the CHC22 effect on neural differentiation is independent of the more
common clathrin heavy chain CHC17, and that CHC22-dependent differentiation is mediated
through an autocrine/paracrine mechanism. Using quantitative proteomics, we define the
composition of clathrin-coated vesicles in SH-SY5Y cells, and determine proteome changes
induced by CHC22 depletion. In the absence of CHC22 a subset of dense core granule (DCG)
neuropeptides accumulated, were processed into biologically active ‘mature’ forms, and
secreted in sufficient quantity to trigger neural differentiation. When CHC22 is present,
however, these DCG neuropeptides are directed to the lysosome and degraded, thus
preventing differentiation. This suggests that the brief reduction seen in CHC22 expression in
sensory neural precursors may license a step in neuron precursor neurodevelopment; and that
this step is mediated through control of a novel neuropeptide processing pathway.
Keywords
Neurons, Cell Line, Tumor, Lysosomes, Humans, Neuropeptides, Clathrin Heavy Chains, Autocrine Communication, Paracrine Communication, Cell Differentiation, Protein Transport, Gene Knockdown Techniques, Proteolysis
Sponsorship
MRC (MR/J012742/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1415-50)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1038/s41598-018-19980-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/273997
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