perlecan

Perlecan, also known as heparan sulfate proteoglycan 2 (HSPG2), is a large secreted protein of the basement membrane family. It is a core component of extracellular matrices in many tissues and is characterized by covalently attached heparan sulfate glycosaminoglycan chains. The core protein is organized into multiple modules, commonly described as five domains (I–V), with Domain I bearing the sites for HS chain attachment. The remaining domains comprise laminin-like and other motifs that contribute to interactions with basement membrane components and growth factors.

Localization and structure: Perlecan is widely distributed in basement membranes, particularly within vasculature, cartilage, kidney glomeruli, and other epithelia. It interacts with major basement membrane components such as laminin, collagen IV, and nidogen, helping to organize and stabilize the structural scaffold. The heparan sulfate chains on perlecan bind a broad range of signaling molecules, including fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF), thereby concentrating and modulating signaling events at the cell surface.

Functions: By providing structural support and regulating the availability of growth factors, perlecan influences cell adhesion, migration, angiogenesis, and tissue development. It plays a critical role in vascular integrity and skeletal development, and its proper function is important for endochondral ossification and basement membrane assembly.

Clinical significance: Mutations in HSPG2, the gene encoding perlecan, cause inherited disorders such as Schwartz-Jampel syndrome type 1 and dyssegmental dysplasia Silverman-Handmaker, a severe neonatal skeletal dysplasia. The protein is also studied for its roles in wound healing, tumor biology, and tissue engineering.

Research and applications: Ongoing work investigates domain-specific functions, growth factor interactions, and therapeutic potential of perlecan and its fragments in regenerative medicine and cancer.