Synemin is a unique cytoplasmic intermediate filament protein for which there is 
limited understanding of its exact cellular functions. The single human synemin 
gene encodes at least two splice variants named alpha-synemin and beta-synemin, 
with the larger alpha-synemin containing an additional 312 amino acid insert 
within the C-terminal tail domain. We report herein that, by using the entire 
tail domain of the smaller beta-synemin as the bait in a yeast two-hybrid screen 
of a human skeletal muscle cDNA library, the LIM domain protein zyxin was 
identified as an interaction partner for human synemin. The synemin binding site 
in human zyxin was subsequently mapped to the C-terminal three tandem LIM-domain 
repeats, whereas the binding site for zyxin within beta-synemin is within the 
C-terminal 332 amino acid region (SNbetaTII) at the end of the long tail domain. 
Transient expression of SNbetaTII within mammalian cells markedly reduced zyxin 
protein level, blocked localization of zyxin at focal adhesion sites and 
resulted in decreased cell adhesion and increased motility. Knockdown of synemin 
expression with siRNAs within mammalian cells resulted in significantly 
compromised cell adhesion and cell motility. Our results suggest that synemin 
participates in focal adhesion dynamics and is essential for cell adhesion and 
migration.