Organizing Motility

Abstract

See related article, pages 378–385 Vascular smooth muscle cells (SMCs) acquire a highly specialized cytoskeleton during development that is organized for efficient transmission of contractile force. This SMC cytoskeleton must be extensively reorganized to support directed cell migrations that are required for repair of arterial injury. Particularly important in this reorganization process are adaptor proteins that mediate the assembly of multiprotein complexes involved in cell adhesion, lamellipodial extensions, signal transduction, and transcriptional activation. One such adaptor protein is called lipoma-preferred partner (LPP), a member of the LIM domain–containing protein family, most closely related to zxyin, ajuba, LIM domain–containing protein-1 (LIMD1), and thyroid receptor-interacting protein-6 (TRIP6).1 Evidence to suggest that LPP is a smooth muscle–restricted LIM protein that plays an important role in SMC migration after arterial injury is reported by Gorenne et al in this issue of Circulation Research .2 LPP was discovered as a component of t(3:12) chromosome translocations found in benign tumors of human adipose tissue (lipomas).3 The chromosome 3 breakpoint occurred in a 400-kb genomic locus that encoded a protein with proline-rich sequences and leucine zipper motifs at its N terminus and three LIM domains at its C terminus. The t(3:12) translocation produced a fusion protein containing the N-terminal DNA binding domain of HMGIC fused to the C-terminal LIM domains of a protein encoded by the chromosome 3 locus. The latter was given the name LIM domain–containing lipoma-preferred partner (LPP).3 The lipoma-associated fusion protein is localized to the nucleus4 and can function as a transcription activator.5 Translocations involving the LIM domains of LPP are the most common chromosomal translocations found in human tumors. In addition to lipomas, they have been found in various benign and malignant tumors of mesenchymal origin, including leukemias (fused with the mixed lineage leukemia protein (MLL), …