Cogo, Susanna;
Tomkins, James E;
Vavouraki, Nikoleta;
Giusti, Veronica;
Forcellato, Federica;
Franchin, Cinzia;
Tessari, Isabella;
... Greggio, Elisa; + view all
(2022)
Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins.
Neurobiology of Disease
, 174
, Article 105858. 10.1016/j.nbd.2022.105858.
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Abstract
Mutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning of the corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through the formation of a coat-like complex and its loss of function results in lysosomal and axonal transport impairments. However, the upstream mechanisms that regulate spatacsin trafficking are unknown. Here, using proteomics and CRISPR/Cas9-mediated tagging of endogenous spatacsin, we identified a subset of 14-3-3 proteins as physiological interactors of spatacsin. The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955, which initiates spatacsin trafficking from the plasma membrane to the intracellular space. Our study provides novel insight in understanding spatacsin physio-pathological roles with mechanistic dissection of its associated pathways.
| Type: | Article |
|---|---|
| Title: | Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nbd.2022.105858 |
| Publisher version: | https://doi.org/10.1016/j.nbd.2022.105858 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | 14–3-3 s, Hereditary spastic paraplegia (HSP), Intracellular trafficking, Protein Kinase A (PKA), Protein-protein interactions (PPI), SPG11/Spatacsin |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10156483 |
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