Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

Abstract

Leucine-rich repeats (LRRs) are motifs that form protein-ligand interaction domains. There are approximately 140 human genes encoding proteins with extracellular LRRs. These encode cell adhesion molecules (CAMs), proteoglycans, G-protein-coupled receptors, and other types of receptors. Here we give a brief description of 36 proteins with extracellular LRRs that all can be characterized as CAMs or putative CAMs expressed in the nervous system. The proteins are involved in multiple biological processes in the nervous system including the proliferation and survival of cells, neuritogenesis, axon guidance, fasciculation, myelination, and the formation and maintenance of synapses. Moreover, the proteins are functionally implicated in multiple diseases including cancer, hearing impairment, glaucoma, Alzheimer's disease, multiple sclerosis, Parkinson's disease, autism spectrum disorders, schizophrenia, and obsessive-compulsive disorders. Thus, LRR-containing CAMs constitute a large group of proteins of pivotal importance for the development, maintenance, and regeneration of the nervous system.

Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation

“…Homotypic axon fasciculation is largely mediated by adhesion molecules that must be secreted to the surface of axonstoengage one another via extracellular domains ( Winther and Walmod, 2014 ). Based on our findings that cells only expressing TFG (p.R106C)exhibitdefectsincargotransportfromtheER,wespeculated that the defect in axon bundling may result from impaired trafficking of adhesion molecules.…”

Tinospora cordifolia ameliorates anxiety-like behavior and improves cognitive functions in acute sleep deprived rats

“…Further experiments to discern the underlying molecular mechanism for the differences in the behavioral trends for all the three test groups revealed enhanced expression of synaptic plasticity markers PSA-NCAM and NCAM in VSD group. Despite, being the key molecules for regulating structural plasticity in brain regions like hippocampus and pyriform cortex 19 (which are associated with learning and memory behavior), their expression has been found to be upregulated under various stress conditions and mood disorders, including juvenile 20 and chronic stress like restraining 21 . As VSD animals showed enhanced PSA-NCAM and NCAM expression in hippocampus as compared to VUD group, this increase may be the result of compensatory mechanisms to overcome the stress and to retain the structural and functional integrity and neural networking.…”

Keratan sulfate, a complex glycosaminoglycan with unique functional capability

“…The SLRP family contains a number of KSPGs which regulate signaling pathways in neural development and in neural maintenance ( Dellett et al 2012 ). A distinguishing feature of the SLRPs is their central LRRs which adopt a horseshoe-like configuration which facilitates protein–protein interactions ( Kobe and Deisenhofer 1994 ; Scott 1996 ; Iozzo 1997 ) and molecular recognition processes, including cell adhesion, signal transduction and DNA repair ( Hocking et al 1998 ; Schonherr and Hausser 2000 ; Wei et al 2008 ; Winther and Walmod 2014 ) (Figure 3 ). LRRs are present in more than 6000 proteins ( Wei et al 2008 ) and approximately 140 genes encode extracellular LRR proteins ( Winther and Walmod 2014 ).…”

“…A distinguishing feature of the SLRPs is their central LRRs which adopt a horseshoe-like configuration which facilitates protein–protein interactions ( Kobe and Deisenhofer 1994 ; Scott 1996 ; Iozzo 1997 ) and molecular recognition processes, including cell adhesion, signal transduction and DNA repair ( Hocking et al 1998 ; Schonherr and Hausser 2000 ; Wei et al 2008 ; Winther and Walmod 2014 ) (Figure 3 ). LRRs are present in more than 6000 proteins ( Wei et al 2008 ) and approximately 140 genes encode extracellular LRR proteins ( Winther and Walmod 2014 ). The GAG chains of SLRPs function in the maintenance of the spacing of collagen fibers, normal tissue hydration, and interact with growth factors and their receptors ( Kobe and Deisenhofer 1994 ; Scott 1996 ; Iozzo 1997 ; Schonherr and Hausser 2000 ).…”