TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity.

Talin-1 is the core mechanosensitive adapter protein linking integrins to the cytoskeleton. The TLN1 gene is comprised of 57 exons that encode the 2,541 amino acid TLN1 protein. TLN1 was previously considered to be expressed as a single isoform. However, through differential pre-mRNA splicing analysis, we discovered a cancer-enriched, non-annotated 51-nucleotide exon in TLN1 between exons 17 and 18, which we refer to as exon 17b. TLN1 is comprised of an N-terminal FERM domain, linked to 13 force-dependent switch domains, R1-R13. Inclusion of exon 17b introduces an in-frame insertion of 17 amino acids immediately after Gln665 in the region between R1 and R2 which lowers the force required to open the R1-R2 switches potentially altering downstream mechanotransduction. Biochemical analysis of this isoform revealed enhanced vinculin binding, and cells expressing this variant show altered adhesion dynamics and motility. Finally, we showed that the TGF-ß/SMAD3 signaling pathway regulates this isoform switch. Future studies will need to consider the balance of these two TLN1 isoforms.

Vertical structure of the bacterial diversity in meromictic Fayetteville Green Lake.

The permanently stratified water columns in euxinic meromictic lakes produce niche environments for phototrophic sulfur oxidizers and diverse sulfur metabolisms. While Green Lake (Fayetteville, New York, NY) is known to host a diverse community of ecologically important sulfur bacteria, analyses of its microbial communities, to date, have been largely based on pigment analysis and smaller datasets from Sanger sequencing techniques. Here, we present the results of next-generation sequencing of the eubacterial community in the context of the water column geochemistry. We observed abundant purple and green sulfur bacteria, as well as anoxygenic photosynthesis-capable cyanobacteria within the upper monimolimnion. Amidst the phototrophs, we found other sulfur-cycling bacteria including sulfur disproportionators and chemotrophic sulfur oxidizers, further detailing our understanding of the sulfur cycle and microbial ecology of euxinic, meromictic lakes.