Perlecan Protein Core Interacts with Extracellular Matrix Protein 1 (ECM1), a Glycoprotein Involved in Bone Formation and Angiogenesis

Abstract

The goal of this study was to discover novel partners for perlecan, a major heparan sulfate proteoglycan of basement membranes, and to examine new interactions through which perlecan may influence cell behavior. We employed the yeast two-hybrid system and used perlecan domain V as bait to screen a human keratinocyte cDNA library. Among the strongest interacting clones, we isolated a ϳ1.6-kb cDNA insert that encoded extracellular matrix protein 1 (ECM1), a secreted glycoprotein involved in bone formation and angiogenesis. The sequencing of the clone revealed the existence of a novel splice variant that we name ECM1c. The interaction was validated by co-immunoprecipitation studies, using both cell-free systems and mammalian cells, and the specific binding site within each molecule was identified employing various deletion mutants. The C terminus of ECM1 interacted specifically with the epidermal growth factor-like modules flanking the LG2 subdomain of perlecan domain V. Perlecan and ECM1 were also co-expressed by a variety of normal and transformed cells, and immunohistochemical studies showed a partial expression overlap, particularly around dermal blood vessels and adnexal epithelia. ECM1 has been shown to regulate endochondral bone formation, stimulate the proliferation of endothelial cells, and induce angiogenesis. Similarly, perlecan plays an important role in chondrogenesis and skeletal development, as well as harboring pro-and anti-angiogenic activities. Thus, a physiological interaction could also occur in vivo during development and in pathological events, including tissue remodeling and tumor progression.

WARP Is a Novel Multimeric Component of the Chondrocyte Pericellular Matrix That Interacts with Perlecan

“…The perlecan core protein has been shown to associate with a range of basement membrane macromolecules including collagens (IV and XIII), laminin-1, nidogens 1 and 2, ␤1-integrin, ␣-dystroglycan, as well as fibulin-2, fibrillin-1, ECM-1, PRELP (proline-arginine-rich end leucine-rich repeat protein), fibronectin, heparin, and several growth factors (platelet-derived growth factor, FGF-2, FGF-7) and FGF-binding protein (19,(32)(33)(34)(35)(36)(37).…”

What maintains the high intra-follicular estradiol concentration in pre-ovulatory follicles?

“…This is a powerful angiostatic agent capable of inhibiting several aspects of angiogenesis: endothelial cell migration, collageninduced endothelial tube morphogenesis, and blood vessel growth [53]. The presence of perlecan in the FF and GC is likely the mechanism that keeps the follicle avascular until ovulation.…”

Síndrome de Urbach-Wiethe: relato de caso

“…impacto na dinâmica de diferenciação dos queratinócitos, alterando seu padrão normal de maturação e levando à hiperqueratose. Na derme pode agir como "cola biológica" para glicosaminoglicanos e como fator de crescimento (14) . A perda do ECM1 pode ter efeito na homeostase dermal causando infiltração cutânea e as alterações dermatopatológicas da hialinose.…”