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Cellular and Molecular Life Sciences :... Mar 2017Laminin, one of the most widely expressed extracellular matrix proteins, exerts many important functions in multiple organs/systems and at various developmental stages.... (Review)
Review
Laminin, one of the most widely expressed extracellular matrix proteins, exerts many important functions in multiple organs/systems and at various developmental stages. Although its critical roles in embryonic development have been demonstrated, laminin's functions at later stages remain largely unknown, mainly due to its intrinsic complexity and lack of research tools (most laminin mutants are embryonic lethal). With the advance of genetic and molecular techniques, many new laminin mutants have been generated recently. These new mutants usually have a longer lifespan and show previously unidentified phenotypes. Not only do these studies suggest novel functions of laminin, but also they provide invaluable animal models that allow investigation of laminin's functions at late stages. Here, I first briefly introduce the nomenclature, structure, and biochemistry of laminin in general. Next, all the loss-of-function mutants/models for each laminin chain are discussed and their phenotypes compared. I hope to provide a comprehensive review on laminin functions and its loss-of-function models, which could serve as a reference for future research in this understudied field.
Topics: Animals; Humans; Laminin; Protein Isoforms; Terminology as Topic
PubMed: 27696112
DOI: 10.1007/s00018-016-2381-0 -
The International Journal of... Aug 1999Laminins are a family of glycoproteins which are ubiquitous components of basement membranes and play key structural and functional roles. Eleven isoforms have been... (Review)
Review
Laminins are a family of glycoproteins which are ubiquitous components of basement membranes and play key structural and functional roles. Eleven isoforms have been identified to date; each is an alpha beta gamma heterotrimer assembled from a repertoire of five alpha, three beta and two gamma chains. Studies of laminin-11 (alpha 5 beta 2 gamma 1) illustrate the unique expression patterns and distinct functions that can be displayed by laminin isoforms. Laminin-11 is found in the glomerular basement membrane in kidney, in the neuromuscular synaptic cleft in skeletal muscle and in other tissues such as placenta and lung. Mice lacking laminin-11 exhibit defective glomerular filtration and developmental defects in neuromuscular synapse formation, with Schwann cells invading the synaptic cleft. Consistent with these observations, both motoneurons and Schwann cells distinguish laminin-11 from other isoforms in vitro. These results suggest that laminin-11 is a structural component of the basement membrane which influences cell behavior in physiologically relevant ways. A greater understanding of laminin-11 assembly and basement membrane incorporation could provide a logical basis for therapy in merosin-deficient congenital muscular dystrophy.
Topics: Animals; Basement Membrane; Laminin; Muscular Dystrophies; Neuromuscular Junction; Protein Conformation; Protein Isoforms
PubMed: 10481268
DOI: 10.1016/s1357-2725(99)00030-8 -
Cell Adhesion & Migration 2013Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the α, β and γ chains. The human genome encodes... (Review)
Review
Laminins are large molecular weight glycoproteins constituted by the assembly of three disulfide-linked polypeptides, the α, β and γ chains. The human genome encodes 11 genetically distinct laminin chains. Structurally, laminin chains differ by the number, size and organization of a few constitutive domains, endowing the various members of the laminin family with common and unique important functions. In particular, laminins are indispensable building blocks for cellular networks physically bridging the intracellular and extracellular compartments and relaying signals critical for cellular behavior, and for extracellular polymers determining the architecture and the physiology of basement membranes.
Topics: Animals; Basement Membrane; Binding Sites; Cell Adhesion; Cell Adhesion Molecules; Extracellular Matrix; Humans; Laminin; Molecular Weight; Protein Conformation; Protein Folding; Protein Interaction Mapping; Protein Structure, Tertiary; Receptors, Laminin; Signal Transduction
PubMed: 23263632
DOI: 10.4161/cam.22826 -
Pharmacology & Therapeutics Oct 2019Recently, the development of drug delivery systems (DDSs) for clinical application of anticancer drugs and gene therapy has rapidly progressed. In particular, DDS... (Review)
Review
Recently, the development of drug delivery systems (DDSs) for clinical application of anticancer drugs and gene therapy has rapidly progressed. In particular, DDS carriers used for chemotherapy and gene therapy are required to selectively deliver drugs and genes to cancer cells. Both the carrier and the molecule must in combination be highly selective in most cases. Possible candidate targeting molecules are the laminins, major basement membrane proteins that interact with various cells through their multiple constituent active peptide sequences. Laminin-derived peptides bind to various cellular receptors and have been used for DDSs as a targeting moiety. Here, we review the progress in laminin-derived peptide-conjugated DDSs. Drug and gene carriers as well as ultrasound diagnostic contrast agents utilizing laminin-derived peptides for selective targeting are useful components of DDSs and play important roles in cancer and in the neovasculature.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Laminin; Neoplasms; Peptides
PubMed: 31158392
DOI: 10.1016/j.pharmthera.2019.05.017 -
Matrix Biology : Journal of the... Oct 2018Laminins are large heterotrimers composed of the α, β and γ subunits with distinct tissue-specific and developmentally regulated expression patterns. The laminin-α2... (Review)
Review
Laminins are large heterotrimers composed of the α, β and γ subunits with distinct tissue-specific and developmentally regulated expression patterns. The laminin-α2 subunit, encoded by the LAMA2 gene, is expressed in skeletal muscle, Schwann cells of the peripheral nerve and astrocytes and pericytes of the capillaries in the brain. Mutations in LAMA2 cause the most common type of congenital muscular dystrophies, called LAMA2 MD or MDC1A. The disorder manifests mostly as a muscular dystrophy but slowing of nerve conduction contributes to the disease. There are severe, non-ambulatory or milder, ambulatory variants, the latter resulting from reduced laminin-α2 expression and/or deficient laminin-α2 function. Lm-211 (α2β1γ1) is responsible for initiating basement membrane assembly. This is primarily accomplished by anchorage of Lm-211 to dystroglycan and α7β1 integrin receptors, polymerization, and binding to nidogen and other structural components. In LAMA2 MD, Lm-411 replaces Lm-211; however, Lm-411 lacks the ability to polymerize and bind to receptors. This results in a weakened basement membrane leading to the disease. The possibility of introducing structural repair proteins that correct the underlying abnormality is an attractive therapeutic goal. Recent studies in mouse models for LAMA2 MD reveal that introduction of laminin-binding linker proteins that restore lost functional activities can substantially ameliorate the disease. This review discusses the underlying mechanism of this repair and compares this approach to other developing therapies employing pharmacological treatments.
Topics: Animals; Basement Membrane; Dystroglycans; Humans; Integrins; Laminin; Membrane Glycoproteins; Mice; Muscular Dystrophies; Mutation; Protein Binding
PubMed: 29191403
DOI: 10.1016/j.matbio.2017.11.009 -
Current Opinion in Cell Biology Oct 1993During the preceding year significant progress has been made in our understanding of laminin structure and expression. Highlights include the identification of new... (Review)
Review
During the preceding year significant progress has been made in our understanding of laminin structure and expression. Highlights include the identification of new subunit chains and molecular isoforms as well as new information on tissue-specific gene expression, laminin self-assembly and interactions with other matrix components.
Topics: Animals; Basement Membrane; Genetic Variation; Humans; Laminin; Models, Structural
PubMed: 8240830
DOI: 10.1016/0955-0674(93)90038-r -
Archives of Oral Biology Aug 2016To our knowledge from indexed literature, the role of laminins in the expression of osteogenic biomarkers and osseointegration enhancement has not been systematically... (Review)
Review
To our knowledge from indexed literature, the role of laminins in the expression of osteogenic biomarkers and osseointegration enhancement has not been systematically reviewed. The aim of the present systematic review was to assess the role of laminin coatings on implant surfaces in promoting osseointegration. To address the focused question, "Do laminin coatings on implant surfaces influence osseointegration?", indexed databases were searched from 1965 up to and including November 2015 using various combination of the following keywords: "Bone to implant contact"; "implant"; "laminins"; and "osseointegration". Letters to the Editor, case-reports/case-series, historic reviews, and commentaries were excluded. The pattern of the present systematic review was customized to primarily summarize the pertinent data. Nine studies were included. Six studies were prospective and were performed in animals and 5 studies were in vitro. Results from 8 studies showed that laminin coatings enhanced new bone formation around implants and/or bone-to-implant contact. One study showed that laminin coated implants surfaces did not improve osseointegration. On experimental grounds, laminin coatings seem to enhance osteogenic biomarkers expression and/or osseointegration; however, from a clinical perspective, further randomized control trials are needed to assess the role of laminin coatings in promoting osseointegration around dental implants.
Topics: Animals; Coated Materials, Biocompatible; Dental Implantation, Endosseous; Dental Implants; Humans; Laminin; Osseointegration; Osteogenesis; Prospective Studies; Surface Properties; Titanium
PubMed: 27164563
DOI: 10.1016/j.archoralbio.2016.05.005 -
Journal of Cellular Biochemistry Jun 1996Extracellular matrix molecules are often very large and made up of several independent domains, frequently with autonomous activities. Laminin is no exception. A number... (Review)
Review
Extracellular matrix molecules are often very large and made up of several independent domains, frequently with autonomous activities. Laminin is no exception. A number of globular and rod-like domains can be identified in laminin and its isoforms by sequence analysis as well as by electron microscopy. Here we present the structure-function relations in laminins by examination of their individual domains. This approach to viewing laminin is based on recent results from several laboratories. First, some mutations in laminin genes that cause disease have affected single laminin domains, and some laminin isoforms lack particular domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. These mutants and isoforms are informative with regard to the activities of the mutated and missing domains. Second, laminin-like domains have now been found in a number of other proteins, and data on these proteins may be informative in terms of structure-function relationships in laminin. Finally, a large body of data has accumulated on the structure and activities of proteolytic fragments, recombinant fragments, and synthetic peptides from laminin. The proposed activities of these domains can now be confirmed and extended by in vivo experiments.
Topics: Animals; Humans; Laminin; Polymers; Protein Structure, Secondary; Protein Structure, Tertiary; Structure-Activity Relationship
PubMed: 8806072
DOI: 10.1002/(SICI)1097-4644(19960616)61:4%3C493::AID-JCB2%3E3.0.CO;2-J -
Current Topics in Membranes 2015Laminins are composed of three polypeptide chains, designated as α, β, and γ. The C-terminal region of laminin heterotrimers, containing coiled-coil regions, short... (Review)
Review
Laminins are composed of three polypeptide chains, designated as α, β, and γ. The C-terminal region of laminin heterotrimers, containing coiled-coil regions, short tails, and laminin globular (LG) domains, is necessary and sufficient for binding to integrins, which are the major laminin receptor class. Laminin recognition by integrins critically requires the α chain LG domains and a glutamic acid residue of the γ chain at the third position from the C-terminus. Furthermore, the C-terminal region of the β chain contains a short amino acid sequence that modulates laminin affinity for integrins. Thus, all three of the laminin chains act cooperatively to facilitate integrin binding. Mammals possess 5 α (α1-5), 3 β (β1-3), and 3 γ (γ1-3) chains, combinations of which give rise to 16 distinct laminin isoforms. Each isoform is expressed in a tissue-specific and developmental stage-specific manner, exerting its functions through binding of integrins. In this review, we detail the current knowledge surrounding the molecular basis and physiological relevance of specific interactions between laminins and integrins, and describe the mechanisms underlying laminin action through integrins.
Topics: Animals; Humans; Integrins; Laminin; Protein Binding; Receptors, Laminin; Substrate Specificity; Tetraspanins
PubMed: 26610915
DOI: 10.1016/bs.ctm.2015.07.002 -
Trends in Neurosciences Jul 1989The ability of the extracellular matrix protein laminin to regulate the survival and differentiation of neurons has led to the search for a neuronal laminin receptor.... (Review)
Review
The ability of the extracellular matrix protein laminin to regulate the survival and differentiation of neurons has led to the search for a neuronal laminin receptor. This article reviews the evidence for the existence of laminin receptors, and then goes on to discuss the difficulties in making the jump from a pharmacological demonstration of the receptor to its molecular identification.
Topics: Animals; Laminin; Receptors, Immunologic; Receptors, Laminin
PubMed: 2475934
DOI: 10.1016/0166-2236(89)90020-9