10.1371/journal.pgen.1008665
Yoan Arribat
Yoan
Arribat
Dogan Grepper
Dogan
Grepper
Sylviane Lagarrigue
Sylviane
Lagarrigue
Timothy Qi
Timothy
Qi
Sarah Cohen
Sarah
Cohen
Francesca Amati
Francesca
Amati
Spastin mutations impair coordination between lipid droplet dispersion and reticulum
Public Library of Science
2020
Spastin depletion
results show
HSP
Spastin M 1
Spastin mutations
novel biomarkers
organelle components
system results
intracellular dispersion
lipid droplet dispersion
organelle dynamics
Hereditary Spastic Paraplegia
MT
coordinates LD dispersion
Spastin modulates transcripts levels
m 1 isoforms
splice variants
endoplasmic reticulum
reticulum Lipid droplets
REEP 1.
ER shape
impacts lipids profile
impact LD fate
subcellular location
Spastin depletion influences
LD dispersion
impacts LD network
2020-04-21 22:05:44
Dataset
https://plos.figshare.com/articles/dataset/Spastin_mutations_impair_coordination_between_lipid_droplet_dispersion_and_reticulum/12170220
<div><p>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.</p></div>