PUBLICATION

Spastin mutations impair coordination between lipid droplet dispersion and reticulum

Authors
Arribat, Y., Grepper, D., Lagarrigue, S., Qi, T., Cohen, S., Amati, F.
ID
ZDB-PUB-200422-174
Date
2020
Source
PLoS Genetics   16: e1008665 (Journal)
Registered Authors
Amati, Francesca, Arribat, Yoan, Grepper, Dogan, Lagarrigue, Silviane
Keywords
none
MeSH Terms
  • Cells, Cultured
  • GTP-Binding Protein gamma Subunits/metabolism
  • Animals
  • Humans
  • Membrane Transport Proteins/metabolism
  • Zebrafish
  • Endoplasmic Reticulum/metabolism*
  • Lipid Droplets/metabolism*
  • HeLa Cells
  • Protein Binding
  • Microtubules/metabolism
  • Spastin/genetics
  • Spastin/metabolism*
(all 13)
PubMed
32315314 Full text @ PLoS Genet.
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.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ula1
    Small Deletion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    spastCRISPR3-spastCRISPR
    1 - 1 of 1
    Show
    Fish
    1 - 2 of 2
    Show
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available