Abstract
Perlecan has multiple functions in cell growth and differentiation and tissue homeostasis. Recent studies with mutant mice and human genetic disorders have shed light into the in vivo functions of perlecan. Complete deficiency of perlecan results in embryonic and perinatal lethality with severe defects in cartilage, cephalic development and cardiovascular systems. In adult tissues, perlecan is essential for high density clustering of acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) and partially functional mutations of perlecan result in myotonia and milder chondrodysplasia. Deletion of a short coding sequence including the HS attachment sites of the N-terminus of perlecan in mice revealed that the HS chains are not essential for development but play a role in supporting the integrity of the lens capsule, in promoting angiogenesis and tumor growth, and filtration in the kidney. In vitro studies indicate that many extracellular molecules and cell surface receptors interact with the HS chains and core protein of perlecan. Perlecan may work as a modulator for growth factor signaling and a ligand reservoir.
