Spastin mutations impair coordination between lipid droplet dispersion and reticulum.

Details

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State: Public
Version: Final published version
License: CC BY-ND 4.0
Serval ID
serval:BIB_A8167CF70446
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Spastin mutations impair coordination between lipid droplet dispersion and reticulum.
Journal
PLoS genetics
Author(s)
Arribat Y., Grepper D., Lagarrigue S., Qi T., Cohen S., Amati F.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
04/2020
Peer-reviewed
Oui
Volume
16
Number
4
Pages
e1008665
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Lipid droplets (LD) are affected in multiple human disorders. These highly dynamic organelles are involved in many cellular roles. While their intracellular dispersion is crucial to ensure their function and other organelles-contact, underlying mechanisms are still unclear. Here we show that Spastin, one of the major proteins involved in Hereditary Spastic Paraplegia (HSP), controls LD dispersion. Spastin depletion in zebrafish affects metabolic properties and organelle dynamics. These functions are ensured by a conserved complex set of splice variants. M1 isoforms determine LD dispersion in the cell by orchestrating endoplasmic reticulum (ER) shape along microtubules (MTs). To further impact LD fate, Spastin modulates transcripts levels and subcellular location of other HSP key players, notably Seipin and REEP1. In pathological conditions, mutations in human Spastin M1 disrupt this mechanism and impacts LD network. Spastin depletion influences not only other key proteins but also modulates specific neutral lipids and phospholipids, revealing an impact on membrane and organelle components. Altogether our results show that Spastin and its partners converge in a common machinery that coordinates LD dispersion and ER shape along MTs. Any alteration of this system results in HSP clinical features and impacts lipids profile, thus opening new avenues for novel biomarkers of HSP.
Keywords
Animals, Cells, Cultured, Endoplasmic Reticulum/metabolism, GTP-Binding Protein gamma Subunits/metabolism, HeLa Cells, Humans, Lipid Droplets/metabolism, Membrane Transport Proteins/metabolism, Microtubules/metabolism, Protein Binding, Spastin/genetics, Spastin/metabolism, Zebrafish
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Projects / 320030_170062
Create date
22/04/2020 11:58
Last modification date
14/08/2020 5:21
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