Cytoplasmic inclusions containing TAR DNA-binding protein of 43 kDa (TDP-43) or 
Fused in sarcoma (FUS) are a hallmark of amyotrophic lateral sclerosis (ALS) and 
several subtypes of frontotemporal lobar degeneration (FTLD). FUS-positive 
inclusions in FTLD and ALS patients are consistently co-labeled with stress 
granule (SG) marker proteins. Whether TDP-43 inclusions contain SG markers is 
currently still debated. We determined the requirements for SG recruitment of 
FUS and TDP-43 and found that cytoplasmic mislocalization is a common 
prerequisite for SG recruitment of FUS and TDP-43. For FUS, the 
arginine-glycine-glycine zinc finger domain, which is the protein's main RNA 
binding domain, is most important for SG recruitment, whereas the glycine-rich 
domain and RNA recognition motif (RRM) domain have a minor contribution and the 
glutamine-rich domain is dispensable. For TDP-43, both the RRM1 and the 
C-terminal glycine-rich domain are required for SG localization. ALS-associated 
point mutations located in the glycine-rich domain of TDP-43 do not affect SG 
recruitment. Interestingly, a 25-kDa C-terminal fragment of TDP-43, which is 
enriched in FTLD/ALS cortical inclusions but not spinal cord inclusions, fails 
to be recruited into SG. Consistently, inclusions in the cortex of FTLD 
patients, which are enriched for C-terminal fragments, are not co-labeled with 
the SG marker poly(A)-binding protein 1 (PABP-1), whereas inclusions in spinal 
cord, which contain full-length TDP-43, are frequently positive for this marker 
protein.