3 research outputs found
Patients with chronic insomnia have selective impairments in memory that are modulated by cortisol
Reconstitution and Dissection of the 600-kDa Srv2/CAP Complex: ROLES FOR OLIGOMERIZATION AND COFILIN-ACTIN BINDING IN DRIVING ACTIN TURNOVER*
Srv2/cyclase-associated protein is expressed in virtually all plant,
animal, and fungal organisms and has a conserved role in promoting actin
depolymerizing factor/cofilin-mediated actin turnover. This is achieved by the
abilities of Srv2 to recycle cofilin from ADP-actin monomers and to promote
nucleotide exchange (ATP for ADP) on actin monomers. Despite this important
and universal role in facilitating actin turnover, the mechanism underlying
Srv2 function has remained elusive. Previous studies have demonstrated a
critical functional role for the G-actin-binding C-terminal half of Srv2. Here
we describe an equally important role in vivo for the N-terminal half
of Srv2 in driving actin turnover. We pinpoint this activity to a conserved
patch of surface residues on the N-terminal dimeric helical folded domain of
Srv2, and we show that this functional site interacts with cofilin-actin
complexes. Furthermore, we show that this site is essential for Srv2
acceleration of cofilin-mediated actin turnover in vitro. A cognate
Srv2-binding site is identified on a conserved surface of cofilin, suggesting
that this function likely extends to other organisms. In addition, our
analyses reveal that higher order oligomerization of Srv2 depends on its
N-terminal predicted coiled coil domain and that oligomerization optimizes
Srv2 function in vitro and in vivo. Based on these data, we
present a revised model for the mechanism by which Srv2 promotes actin
turnover, in which coordinated activities of its N- and C-terminal halves
catalyze sequential steps in recycling cofilin and actin monomers