Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance

Abstract

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-b and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury.

The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway

“…This stretch is followed by a cysteine cluster with the C-X 3 -C-X-C-X 6 -C pattern, which is conserved among the class I SLRPs ASPN, Biglycan and Decorin, where the second cysteine is replaced by arginine in Xenopus (Fig. 1B) (Dellett et al, 2012). The characteristic stretch of eight leucine-rich repeats was also found to be conserved among vertebrate species.…”

“…This clone encoded a polypeptide sequence similar to human ASPN belonging to the class I family of SLRPs (Dellett et al, 2012), and drawing a phylogenic tree showed that the clone contained a Xenopus orthologue of ASPN (Fig. 1A) (Henry et al, 2001;Lorenzo et al, 2001).…”

“…SLRPs feature leucine-rich repeat domains in the middle of their protein core, and can be categorised into five subclasses depending on their amino acid sequences (Dellett et al, 2012). Whereas most proteoglycans form large heterologous complexes of 300-400 kDa, SLRPs are thought to act mostly as monomers or possibly dimers of ∼40 kDa (Goldoni et al, 2004;McEwan et al, 2006;Scott et al, 2004).…”

“…This activity is exerted through interactions with specific extracellular signalling molecules and/or their receptor proteins. In Xenopus embryogenesis, SLRPs have been shown to play important roles in a number of developmental processes, such as germ layer specification, pattern formation and morphogenesis (Dellett et al, 2012;Kuriyama et al, 2006;Moreno et al, 2005;Muñoz et al, 2006). For instance, Biglycan binds to BMP4 and changes the interaction between BMP4 and Chordin (Moreno et al, 2005).…”

“…The family of small leucine-rich repeat proteoglycan (SLRP) proteins comprises a number of extracellular matrix proteoglycans that have been shown to be involved in a number of biological events, including development, growth and cancer, in recent years (Dellett et al, 2012;Edwards, 2012;Schaefer and Schaefer, 2010). SLRPs feature leucine-rich repeat domains in the middle of their protein core, and can be categorised into five subclasses depending on their amino acid sequences (Dellett et al, 2012).…”