EMAIL THIS PAGE TO A FRIEND

Disease models & mechanisms

ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cell-derived motoneurons.


PMID 26035390

Abstract

Patient-derived induced pluripotent stem cells (iPSCs) provide an opportunity to study human diseases mainly in those cases for which no suitable model systems are available. Here, we have taken advantage of in vitro iPSCs derived from patients affected by amyotrophic lateral sclerosis (ALS) and carrying mutations in the RNA-binding protein FUS to study the cellular behavior of the mutant proteins in the appropriate genetic background. Moreover, the ability to differentiate iPSCs into spinal cord neural cells provides an in vitro model mimicking the physiological conditions. iPSCs were derived from FUS(R514S) and FUS(R521C) patient fibroblasts, whereas in the case of the severe FUS(P525L) mutation, in which fibroblasts were not available, a heterozygous and a homozygous iPSC line were raised by TALEN-directed mutagenesis. We show that aberrant localization and recruitment of FUS into stress granules (SGs) is a prerogative of the FUS mutant proteins and occurs only upon induction of stress in both undifferentiated iPSCs and spinal cord neural cells. Moreover, we show that the incorporation into SGs is proportional to the amount of cytoplasmic FUS, strongly correlating with the cytoplasmic delocalization phenotype of the different mutants. Therefore, the available iPSCs represent a very powerful system for understanding the correlation between FUS mutations, the molecular mechanisms of SG formation and ALS ethiopathogenesis.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB4200511
Anti-FUS (internal region) antibody produced in rabbit, affinity isolated antibody
HPA008784
Anti-FUS antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV40278
Anti-FUS antibody produced in rabbit, affinity isolated antibody
SAB4200454
Anti-FUS antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody
SAB2700785
Anti-FUS antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
G4420 Anti-GRP94 (C-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB4503031
Anti-GRP94, C-Terminal antibody produced in rabbit, affinity isolated antibody
HPA003901
Anti-HSP90B1 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA008424
Anti-HSP90B1 antibody produced in rabbit, Ab2, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV40464
Anti-HSP90B1 antibody produced in rabbit, IgG fraction of antiserum
SAB2101094
Anti-HSP90B1 antibody produced in rabbit, affinity isolated antibody
SAB1412039
ANTI-ISL1 antibody produced in mouse, clone 4A7, purified immunoglobulin, buffered aqueous solution
SAB1412040
ANTI-ISL1 antibody produced in mouse, clone 8A3, purified immunoglobulin, buffered aqueous solution
SAB1412041
ANTI-ISL1 antibody produced in mouse, clone 5F12, purified immunoglobulin, buffered aqueous solution
AV32336
Anti-ISL1 antibody produced in rabbit, affinity isolated antibody, lyophilized powder
HPA057416
Anti-ISL1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1410720
Anti-ISL1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB2101708
Anti-PABPC1 antibody produced in rabbit, affinity isolated antibody
SAB1410526
Anti-PABPC1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1307063
ANTI-PLSCR4 (CENTER) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1407768
Anti-PLSCR4 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA002276
Anti-PLSCR4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2501633
Anti-TIAL1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1409738
Anti-TIAL1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
AV02048
Anti-TIAL1 antibody produced in rabbit, IgG fraction of antiserum
G2536
Ganciclovir, ≥99% (HPLC), powder
C9H13N5O4
PLA0296
Goat anti-FUS Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
SAB4200478
Monoclonal Anti-FUS antibody produced in mouse, clone FUS-4, tissue culture supernatant
AMAB90549
Monoclonal Anti-FUS antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL0190, purified immunoglobulin, buffered aqueous glycerol solution
WH0003670M1
Monoclonal Anti-ISL1 antibody produced in mouse, clone 1A3, purified immunoglobulin, buffered aqueous solution