Thin filament length regulation in striated muscle sarcomeres: Pointed-end dynamics go beyond a nebulin ruler

The actin ( thin). laments in striated muscle are highly regulated and precisely specified in length to optimally overlap with the myosin ( thick). laments for efficient myofibril contraction. Here, we review and critically discuss recent evidence for how thin. lament lengths are controlled in vertebrate skeletal, vertebrate cardiac, and invertebrate ( arthropod) sarcomeres. Regulation of actin polymerization dynamics at the slow-growing ( pointed) ends by the capping protein tropomodulin provides a unified explanation for how thin. lament lengths are physiologically optimized in all three muscle types. Nebulin, a large protein thought to specify thin. lament lengths in vertebrate skeletal muscle through a ruler mechanism, may not control pointed-end actin dynamics directly, but instead may stabilize a large core region of the thin. lament. We suggest that this stabilizing function for nebulin modifies the lengths primarily specified by pointed-end actin dynamics to generate uniform. lament lengths in vertebrate skeletal muscle. We suggest that nebulette, a small homolog of nebulin, may stabilize a correspondingly shorter core region and allow individual thin. lament lengths to vary according to working sarcomere lengths in vertebrate cardiac muscle. We present a unified model for thin. lament length regulation where these two mechanisms cooperate to tailor thin. lament lengths for specific contractile environments in diverse muscles. (c) 2008 Elsevier Ltd. All rights reserved.