Recombinant Mouse 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 mouse LAMA4 cDNA encodes 1815 amino acids (aa), including a 24 aa signal sequence and a 1792 aa mature protein that contains three EGF-like repeats (aa 82 ‑ 240) followed by four coiled-coil regions (aa 431 ‑ 799) and five globular, laminin G‑like (LG) domains (aa 826 ‑ 1813). Two potential isoforms exist, one truncated after Ala885 and the second after Ser679. A protease-sensitive region between LG3 and LG4 produces a processed ~180 kDa form that is detected in vivo (10). Within the LG region, mouse LAMA4 shares 91% and 97% aa identity with the equivalent region of human and rat LAMA4, respectively. 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 the nervous system and the circulation.