A Helix Replacement Mechanism Directs Metavinculin Functions

Cells require distinct adhesion complexes to form contacts with their neighbors or the extracellular matrix, and vinculin links these complexes to the actin cytoskeleton. Metavinculin, an isoform of vinculin that harbors a unique 68-residue insert in its tail domain, has distinct actin bundling and oligomerization properties and plays essential roles in muscle development and homeostasis. Moreover, patients with sporadic or familial mutations in the metavinculin-specific insert invariably develop fatal cardiomyopathies. Here we report the high resolution crystal structure of the metavinculin tail domain, as well as the crystal structures of full-length human native metavinculin (1,134 residues) and of the full-length cardiomyopathy-associated ΔLeu954 metavinculin deletion mutant. These structures reveal that an α-helix (H1′) and extended coil of the metavinculin insert replace α-helix H1 and its preceding extended coil found in the N-terminal region of the vinculin tail domain to form a new five-helix bundle tail domain. Further, biochemical analyses demonstrate that this helix replacement directs the distinct actin bundling and oligomerization properties of metavinculin. Finally, the cardiomyopathy associated ΔLeu954 and Arg975Trp metavinculin mutants reside on the replaced extended coil and the H1′ α-helix, respectively. Thus, a helix replacement mechanism directs metavinculin's unique functions

There's a SNARC in the Size Congruity Task

The size congruity effect involves interference between numerical magnitude and physical size of visually presented numbers: congruent numbers (either both small or both large in numerical magnitude and physical size) are responded to faster than incongruent ones (small numerical magnitude/large physical size or vice versa). Besides, numerical magnitude is associated with lateralized response codes, leading to the Spatial Numerical Association of Response Codes (SNARC) effect: small numerical magnitudes are preferably responded to on the left side and large ones on the right side. Whereas size congruity effects are ascribed to interference between stimulus dimensions in the decision stage, SNARC effects are understood as (in)compatibilities in stimulus-response combinations. Accordingly, size congruity and SNARC effects were previously found to be independent in parity and in physical size judgment tasks. We investigated their dependency in numerical magnitude judgment tasks. We obtained independent size congruity and SNARC effects in these tasks and replicated this observation for the parity judgment task. The results confirm and extend the notion that size congruity and SNARC effects operate in different representational spaces. We discuss possible implications for number representation

There's a SNARC in the Size Congruity Task

The size congruity effect involves interference between numerical magnitude and physical size of visually presented numbers: congruent numbers (either both small or both large in numerical magnitude and physical size) are responded to faster than incongruent ones (small numerical magnitude/large physical size or vice versa). Besides, numerical magnitude is associated with lateralized response codes, leading to the Spatial Numerical Association of Response Codes (SNARC) effect: small numerical magnitudes are preferably responded to on the left side and large ones on the right side. Whereas size congruity effects are ascribed to interference between stimulus dimensions in the decision stage, SNARC effects are understood as (in)compatibilities in stimulus-response combinations. Accordingly, size congruity and SNARC effects were previously found to be independent in parity and in physical size judgment tasks. We investigated their dependency in numerical magnitude judgment tasks. We obtained independent size congruity and SNARC effects in these tasks and replicated this observation for the parity judgment task. The results confirm and extend the notion that size congruity and SNARC effects operate in different representational spaces. We discuss possible implications for number representation