Nebulette interacts with filamin C

Abstract

The actin-binding proteins, nebulette, and nebulin, are comprised of a four-domain layout containing an acidic N-terminal region, a repeat domain, a serine-rich-linker region, and a Src homology-3 domain. Both proteins contain homologous N-terminal regions that are predicted to be in different environments within the sarcomere. The nebulin acidic N-terminal region is found at the distal ends of the thin filaments. Nebulette, however, is predicted to extend 150 nm from the center of the Z-line. To dissect out the functions of the N-terminal domain of nebulette, we have performed a yeast two-hybrid screen using nebulette residues 1-86 as bait. We have identified filamin-C, ZASP-1, and tropomyosin-1 as binding partners. Characterization of the nebulette-filamin interaction indicates that filamin-C predominantly interacts with the modules. These data suggest that filamin-C, a known component of striated muscle Z-lines, interacts with nebulette modules.

Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions with components of the actin and intermediate filament cytoskeleton

“…Because filamin plays an important role in linking the actin cytoskeleton with integrins (Tseng et al 2004;Kiema et al 2006), these results suggest that Hsp27 interactions with filamin could regulate cellmatrix adhesion by regulating signaling between the actin cytoskeleton and extracellular matrix via integrins. Consistent with these results, the actin binding protein nebulette, which was recently shown to interact with filamin C (Holmes and Moncman 2008), also showed increased interaction with Hsp27 in thiolutin-treated cells.…”

Filamin C-related myopathies: pathology and mechanisms

“…FLNc binds essentially two groups of ligands: (1) proteins of the Z-disc including myotilin [17, 56], myopodin [25], the calsarcins [8, 11, 47] and nebulette [21]; (2) sarcolemma-associated proteins such as dystrophin-associated proteins γ-and δ-sarcoglycan [49], the NRAP-talin complex [27], the ponsin-Nck2 complex [14, 61] and β1A integrin [17]. Although often suggested to occur, a direct interaction with the costameric β1D-integrin isoform has been excluded [17].…”

Nebulette Mutations in Cardiac Remodeling

“…Nebulette interacts with a large number of thin filamentassociated and Z-disk-associated proteins (3). The central repeat domains associate with actin, troponin, and tropomyosin; the SH3 domain interacts with actin, ␣-actinin (7), CapZ, titin, myopalladin, zyxin (8), desmin (9), and filamin C (10).…”