The ␤ subunits of voltage-gated Ca 2؉ channels are best known for their roles in regulating surface expression and gating of voltage-gated Ca 2؉ channel ␣ 1 subunits. Recent evidence, however, indicates that these proteins have a variety of Ca 2؉ channel-independent functions. For example, on the molecular level, they regulate gene expression, and on the whole animal level, they regulate early cell movements in zebrafish development. In the present study, an alternatively spliced, truncated ␤4 subunit (␤4c) is identified in the human brain and shown to be highly expressed in nuclei of vestibular neurons. Pulldown assays, nuclear magnetic resonance, and isothermal titration calorimetry demonstrate that the protein interacts with the chromo shadow domain (CSD) of heterochromatin protein 1␥. Site-directed mutagenesis reveals that the primary CSD interaction occurs through a ␤4c C-terminal PXVXL consensus motif, adding the ␤4c subunit to a growing PXVXL protein family with epigenetic responsibilities. These proteins have multiple nuclear functions, including transcription regulation (TIF1␣) and nucleosome assembly (CAF1). An NMR-based two-site docking model of ␤4c in complex with dimerized CSD is presented. Possible roles for the interaction are discussed.Voltage-gated Ca 2ϩ channels play critical roles in a number of cellular events including excitation-contraction coupling, neurotransmitter release, and Ca 2ϩ -dependent gene transcription (1). Voltage-gated Ca 2ϩ channels are multisubunit proteins composed of a pore-forming ␣ 1 subunit, a two-part ␣ 2 ␦/␥ integral membrane subunit, and a soluble cytosolic ␤ subunit (2). The auxiliary ␤ subunit functions both as a chaperone in trafficking the channel complex to the plasma membrane and as a major regulator of channel gating (opening and closing). These functions are thought to occur mainly through a specific interaction between the ␤ subunit and the ␣ 1 interaction domain of the intracellular loop between ␣ 1 repeat motifs I and II (3). More recently, reports of Ca 2ϩ channel-independent functions for ␤ subunits have begun to emerge that appear to be centered in the nucleus. We showed recently, for example, that zebrafish embryos lacking ␤4 subunits failed to initiate epiboly and that the underlying mechanism for this phenomenon may be related to the high levels of ␤4 expression in yolk syncytial nuclei (4). Other studies have shown that ␤ subunit functions in the nucleus may be cell type-and splice variant-specific (5).Voltage-gated Ca 2ϩ channel ␤4 subunit structures are composed of multiple domains. Sequence comparisons led to the initial discovery that Ca 2ϩ channel ␤ subunits are membraneassociated guanylate kinase proteins consisting of core Src homology 3 and guanylate kinase (GK) 2 domains connected by a large variable loop (HOOK) (6). The core is flanked by highly variable N-and C-terminal domains. High resolution x-ray crystallographic studies further confirmed the structure of the ␤ subunit core domains and determined that the interaction between the ␤ an...

The potential use of extracellular matrix (ECM) as a source of wound dressing material has recently received much attention. The ECM is an intricate network of various combinations of elastin, collagens, laminin, fibronectin, and proteoglycans that play a key role in stimulating cell proliferation and differentiation. We evaluated the efficacy of an ECM sheet derived from human adipose tissue as a wound dressing material to enhance healing. We prepared a novel porous ECM sheet dressing scaffold from human adipose tissue. in vitro analysis of the ECM sheets showed efficient decellularisation; absence of immunostimulatory components; and the presence of a wide number of angiogenic and bioactive factors, including collagen, elastin, and proteoglycans. To evaluate in vivo efficacy, full‐thickness excisional wounds were created on the dorsal skin of a rat, and the ECM sheets; secondary healing foam wound dressing, Healoderm; or a conventional dressing were applied to each wound site. Photographs were taken every other day, and the degree of reepithelialisation of the wounds was determined. Application of an ECM sheet dressing enhanced the macroscopic wound‐healing rate on days 4, 7, and 10 compared with that in the control group. Microscopic analysis indicated that the reepithelialisation rate of the wound was higher in the ECM group compared with that in the control group; the reepithelialisation rate was better than that of the secondary healing foam wound dressing. Moreover, a denser and more organised granulation tissue was formed in the ECM sheet group compared with that in the secondary healing foam wound dressing and control groups. The ECM sheet also showed the highest microvessel density compared with the secondary healing foam wound dressing and control groups. Based on these data, we suggest that a bioactive ECM sheet dressing derived from human adipose can provide therapeutic proteins for wound healing.