Looking into laminin receptor: critical discussion regarding the non‐integrin 37/67‐kDalaminin receptor/RPSAprotein

Abstract

The 37/67-kDa laminin receptor (LAMR/RPSA) was originally identified as a 67-kDa binding protein for laminin, an extracellular matrix glycoprotein that provides cellular adhesion to the basement membrane. LAMR has evolutionary origins, however, as a 37-kDa RPS2 family ribosomal component. Expressed in all domains of life, RPS2 proteins have been shown to have remarkably diverse physiological roles that vary across species. Contributing to laminin binding, ribosome biogenesis, cytoskeletal organization, and nuclear functions, this protein governs critical cellular processes including growth, survival, migration, protein synthesis, development, and differentiation. Unsurprisingly given its purview, LAMR has been associated with metastatic cancer, neurodegenerative disease and developmental abnormalities. Functioning in a receptor capacity, this protein also confers susceptibility to bacterial and viral infection. LAMR is clearly a molecule of consequence in human disease, directly mediating pathological events that make it a prime target for therapeutic interventions. Despite decades of research, there are still a large number of open questions regarding the cellular biology of LAMR, the nature of its ability to bind laminin, the function of its intrinsically disordered C-terminal region and its conversion from 37 to 67 kDa. This review attempts to convey an in-depth description of the complexity surrounding this multifaceted protein across functional, structural and pathological aspects.

Improvement of neuronal cell survival by astrocyte‐derived exosomes under hypoxic and ischemic conditions depends on prion protein

“…The laminin receptor with its manifold functions is involved in diverse cellular processes including neuronal survival (for review and references, see DiGiacomo and Meruelo, ). The laminin receptor also plays an important role as PrP receptor in the uptake and propagation of the scrapie PrP form (Kolodziejczak et al, ).…”

Improvement of Cell Penetrating Peptide for Efficient siRNA Targeting of Tumor Xenografts in Zebrafish Embryos

“…Laminin‐1 (LN), a major component of the basal membrane, binds to the 37/67 kDa LR with high affinity . Specifically, the pentapeptide Tyr‐Ile‐Gly‐Ser‐Arg (YIGSR), derived from laminin β1 chain, has been identified as the laminin binding site to its cell surface receptor . The peptide YIGSR has demonstrated its inhibitory effect on tumor growth of several human cancer cell lines and an anti‐metastatic activity in vivo .…”

“…[16] Specifically, the pentapeptide Tyr-Ile-Gly-Ser-Arg (YIGSR), derived from laminin 1 chain, has been identified as the laminin binding site to its cell surface receptor. [17][18][19] The peptide YIGSR has demonstrated its inhibitory effect on tumor growth of several human cancer cell lines and an antimetastatic activity in vivo. [20] These biological properties make the YIGSR peptide an attractive ligand for targeting tumor cells.…”

Target Identification of Kinase Inhibitor Alisertib (MLN8237) by Using DNA‐Programmed Affinity Labeling

“…Laminins (LMNs) are a family of glycoproteins mostly found in the extracellular matrix (ECM) and they play important and diverse roles in regulating cell adhesion, migration, tissue development, and intercellular communications . LAMR, which is the major cell membrane receptor for LMNs, is significantly upregulated in solid tumors and functions as a promoter for cancer metastasis and invasion . Therefore, the identification of LAMR as a potential target may be relevant to the relatively less explored antimigration activity of MLN8237 .…”