Abstract
The aberrant regulation of Wnt secretion is implicated in various neurological diseases. However, the mechanisms of Wnt release are still largely unknown. Here we describe the role of a C. elegans tetraspan protein, HIC-1, in maintaining normal Wnt release. We show that HIC-1 is expressed in cholinergic synapses and that mutants in hic-1 show increased levels of the acetylcholine receptor AChR/ACR-16. Our results suggest that HIC-1 maintains normal AChR/ACR-16 levels by regulating normal Wnt release from presynaptic neurons, as hic-1 mutants show an increase in secreted Wnt from cholinergic neurons. We further show that HIC-1 affects Wnt secretion by modulating the actin cytoskeleton through its interaction with the actin-binding protein NAB-1. In summary, we describe a protein, HIC-1, that functions as a neuromodulator by affecting postsynaptic AChR/ACR-16 levels by regulating presynaptic Wnt release from cholinergic motor neurons. Tikiyani et al. demonstrate that a tetraspan protein, HIC-1, maintains the actin cytoskeleton in C. elegans motor neurons. Loss of hic-1 causes enhanced Wnt secretion from these motor neurons. The findings further reveal mechanisms of Wnt secretion, which is aberrant in certain neuroinflammatory disorders. © 2018 The Author(s)
| Original language | English |
|---|---|
| Pages (from-to) | 1856-1871.e6 |
| Journal | Cell Reports |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 13 Nov 2018 |
| Externally published | Yes |
Bibliographical note
Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].Research Keywords
- C. elegans
- claudin
- F-actin
- Wnt
Publisher's Copyright Statement
- This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/