scholarly journals Epistatic dissection of laminin-receptor interactions in dystrophic zebrafish muscle

2012 ◽  
Vol 21 (21) ◽  
pp. 4718-4731 ◽  
Author(s):  
T. E. Sztal ◽  
C. Sonntag ◽  
T. E. Hall ◽  
P. D. Currie
Keyword(s):  
Laminin Receptor ◽  
Receptor Interactions

scholarly journals Laminin Polymerization Induces a Receptor–Cytoskeleton Network

1999 ◽  
Vol 145 (3) ◽  
pp. 619-631 ◽  
Author(s):  
Holly Colognato ◽  
Donald A. Winkelmann ◽  
Peter D. Yurchenco
Keyword(s):  
Self Assembly ◽  
Receptor Occupancy ◽  
Basement Membranes ◽  
Laminin Receptor ◽  
Cell Surfaces ◽  
Actin Reorganization ◽  
Receptor Interactions ◽  
Cooperative Process ◽  
A Cell ◽  
Receptor Ligation

The transition of laminin from a monomeric to a polymerized state is thought to be a crucial step in the development of basement membranes and in the case of skeletal muscle, mutations in laminin can result in severe muscular dystrophies with basement membrane defects. We have evaluated laminin polymer and receptor interactions to determine the requirements for laminin assembly on a cell surface and investigated what cellular responses might be mediated by this transition. We found that on muscle cell surfaces, laminins preferentially polymerize while bound to receptors that included dystroglycan and α7β1 integrin. These receptor interactions are mediated through laminin COOH-terminal domains that are spatially and functionally distinct from NH2-terminal polymer binding sites. This receptor-facilitated self-assembly drives rearrangement of laminin into a cell-associated polygonal network, a process that also requires actin reorganization and tyrosine phosphorylation. As a result, dystroglycan and integrin redistribute into a reciprocal network as do cortical cytoskeleton components vinculin and dystrophin. Cytoskeletal and receptor reorganization is dependent on laminin polymerization and fails in response to receptor occupancy alone (nonpolymerizing laminin). Preferential polymerization of laminin on cell surfaces, and the resulting induction of cortical architecture, is a cooperative process requiring laminin– receptor ligation, receptor-facilitated self-assembly, actin reorganization, and signaling events.

Recent Advances in the Function of the 67 kDa Laminin Receptor and its Targeting for Personalized Therapy in Cancer

2017 ◽  
Vol 23 (32) ◽  
pp. 4745-4757 ◽  
Author(s):  
Ada Pesapane ◽  
Pia Ragno ◽  
Carmine Selleri ◽  
Nunzia Montuori
Keyword(s):  
Cell Adhesion ◽  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Critical Role ◽  
Protein Translation ◽  
Basement Membranes ◽  
Laminin Receptor ◽  
Cell Surface Receptor ◽  
Future Application ◽  
Neoplastic Cells

The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating cell adhesion, migration, proliferation and survival. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor), is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of the cytoskeleton, such as tubulin and actin. 67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions. 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential. The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression. Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could have a promising future application.

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

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