Recombinant Human Laminin alpha 4 Protein, CF

The alpha 4 chain of laminin (LAMA4) is a secreted ~210 kDa glycoprotein that contributes to the formation of LN411 (laminin-8, subunits alpha 4 beta 1 gamma 1), LN421 (laminin-9, subunits alpha 4 beta 2 gamma 1), and LN423 (laminin-14, subunits alpha 4 beta 2 gamma 3) (1-4). Laminin alpha,  beta  and  gamma  subunits interact via alpha -helical domains to create cruciform, disulfide-linked, coiled-coil laminin heterotrimers (1, 2). LAMA4 is mainly expressed in mesodermal tissues, and is produced by endothelium, cardiac and skeletal muscle fibers, lung mesenchymal cells, pre-adipocytes, kidney mesangial cells, peripheral nerves and neutrophils (3-8). It is found in the subendothelium in muscle, brain, and bone marrow, and in heart, skin, and the perineurium of peripheral nerves (3-7, 9, 10). The human LAMA4 cDNA encodes 1823 amino acids (aa), including a 24 aa signal sequence and a 1799 aa mature protein that contains three EGF-like repeats (aa 82-240) followed by five coiled-coil regions (aa 320-806) and five globular, laminin G-like (LG) domains (aa 833-1820). Potential isoforms of 1816 aa and 1791 aa are lacking sequences following the EGF-like repeats. A protease-sensitive region between LG3 and LG4 produces a processed ~180 kDa form that is detected in vivo (9, 10). Within the LG region, human and mouse LAMA4 share 91% aa sequence identity. LAMA4 LG domains serve as Ca⁺⁺-mediated receptors for integrins such as alpha v beta 3 and alpha 3 beta 1 (mainly at LG2), fibulin-1 and -2 (multiple LG), and heparan sulfate proteoglycans such as syndecans 2 and 4 (mainly at LG4) (8-12). Deletion of LAMA4 in mice results in misalignment of pre- and post-synaptic membranes at neuromuscular junctions, faulty nerve myelination, chronic kidney disease, deficient neutrophil extravasation, and microvessel instability, which causes cardiomyopathy and circulatory dysfunctions (5-8, 12-14). These results show the importance of LAMA4-containing laminins in normal synapse maturation and blood vessel maturation.