Sacsin deletion decreases cell viscoelasticity and motility in a glial cell model of autosomal recessive spastic ataxia of Charlevoix Saguenay
Bibliographic record
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a movement disorder caused by loss-of-function mutations in the sacsin gene. The most common hallmark of this disease is the disruption of intermediate filament networks in cells as diverse as neurons, kidney cells, fibroblasts, astroglia and microglia. Intermediate filaments are the main filaments responsible for the mechanical and viscoelastic properties of cells and tissues, but these have never been investigated in the context of ARSACS. Here, we analyzed the consequences of sacsin loss on the mechanical functions of astroglial-like C6 cells. The phenotype of C6 Sacs−/− cells was analyzed by immunocytochemistry, electron microscopy, mass spectrometry, atomic force microscopy and motility/proliferation assays. C6 Sacs−/− cells presented an abnormal cytoskeletal and organelle distribution, global proteome alterations linked to cell motility and mechanics, a significant decrease in cell elasticity in the cytoplasm, and a striking reduction in cell motility. These mechanical alterations in glial-like cells could be especially relevant for neuroinflammation and glial scar formation upon CNS injury. Our results support a possible role for alterations in glial functions in ARSACS and provide new tools for understanding the glial-specific mechanisms involved in this movement disorder. • Glial-like cells lacking sacsin show proteome-wide mechanical alterations. • Sacsin deletion causes cytoplasmic disorganization of Golgi apparatus and plectin. • Sacsin deletion decreases viscoelasticity in cytoplasmic but not nuclear regions. • Sacsin deletion decreases the motility of cells in culture.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".