TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of 
neurodegenerative disorders, including amyotrophic lateral sclerosis and 
frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is 
an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional 
regulation. Recent work also suggests that TDP-43 associates with cytoplasmic 
stress granules, which are transient structures that form in response to stress. 
In this study, we establish sorbitol as a novel physiological stressor that 
directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We 
quantify the association of TDP-43 with stress granules over time and show that 
stress granule association and size are dependent on the glycine-rich region of 
TDP-43, which harbors the majority of pathogenic mutations. Moreover, we 
establish that cells harboring wild-type and mutant TDP-43 have distinct stress 
responses: mutant TDP-43 forms significantly larger stress granules, and is 
incorporated into stress granules earlier, than wild-type TDP-43; in striking 
contrast, wild-type TDP-43 forms more stress granules over time, but the granule 
size remains relatively unchanged. We propose that mutant TDP-43 alters stress 
granule dynamics, which may contribute to the progression of TDP-43 
proteinopathies.