Peroxide perturbations

In This Issue In This Issue Clash of the titin he sarcomere is more than a complicated piece of structural machinery. According to new results by McElhinny et al. (page 125), a building block of striated muscle cells called MURF-1 may also indirectly regulate gene expression. MURF-1 localizes to sarcomeres thanks to its interaction with titin, a major structural component of the muscle sarcomere, and the largest vertebrate protein identified to date. Titin is anchored at the sarcomere Z-lines, as are thin (actin) filaments. From there it stretches across entire half sarcomeres to overlap at the mid-line (M-line), where it helps anchor thick (myosin) filaments in a central location. Now McElhinny et al. show that different domains of titin perform independent functions. Disturbance of the titin–MURF-1 interaction leads to a complete disruption of M-line and thick filament structure. But the remaining titin regions can still stabilize sarcomeric thin filaments and Z-lines. Then there is the nuclear connection. The authors demonstrate nuclear localization of MURF-1, and interaction with a glucocorticoid-responsive transcriptional activator. Thus, titin may recognize structural alterations in the sarcomere and signal to the nucleus by releasing MURF-1 for translocation to the nucleus and transcriptional activation. A possible mechanism could involve titin phosphorylation of MURF-1, as titin's kinase domain lies adjacent to its MURF-1–binding domain. ᭿ T Sarcomere thick filaments (white) are disrupted by inhibition of titin–MURF-1 binding (right). o understand vision in vertebrates, one might look to worms and algae, according to recent results. On page 103, Pazour et al. show that a T conserved protein transport mechanism in the flagellae of algae and worms is also necessary for development and maintenance of mammalian photoreceptors. Assembly and maintenance of motor and sensory cilia in worms and algae requires the transport of proteins via intraflagellar transport (IFT). The outer segment (OS) of a vertebrate photoreceptor, itself a modified cilium, is formed by transporting membrane and opsin through a connecting cilium that provides a link between the photoreceptor inner (metabolic) and outer (photoreceptive) segments. Photopigment molecules and phototransduction proteins must pass through this connecting cilium to replace components of the OS that have been degraded. Now, it appears that the mechanism used to transport these photoreceptor molecules is conserved throughout eukaryotes. Pazour et al. identified mouse and human homologues of several proteins that form a complex required for IFT in algae. The vertebrate proteins form a complex of similar density to …