Recombinant Mouse CRIM1 Protein, CF

CRIM1 (cysteine-rich motor neuron 1) is a type I transmembrane glycoprotein of the chordin-like cysteine-rich repeat (CRR) family of BMP inhibitors (1 - 4). The ~130 kDa, 1037 amino acid (aa) CRIM1 contains a 34 aa signal sequence, a 906 aa extracellular domain (ECD), a 21 aa transmembrane domain and a 76 aa cytoplasmic domain. The ECD includes an N-terminal IGF-binding protein-like motif and six chordin-like von Willebrand C-type CRRs. The ECD can be released from the cell, presumably by proteolytic processing (4). Mouse CRIM1 ECD shares 88%, 97%, 94%, 93% and 89% aa identity with human, rat, canine, equine and bovine CRIM1 ECD, respectively. CRIM1 CRR domains can interact with several cystine knot-containing growth factors, including VEGF-A, PDGF A and B, and BMPs 2, 4 and 7 (4, 5). It appears to bind VEGF or BMPs intracellularly, and antagonize them by lowering their expression, processing and secretion (4, 5). CRIM1 is expressed in the developing spinal cord in the floor plate and developing motor neurons (1, 6). It is also expressed by perivascular smooth muscle cells and aligns at points of cell-cell contact during endothelial cell capillary formation (2). Endothelial cell expression in vitro appears to be specific to cells that are adherent and growing (2). CRIM1 is also expressed in a spatially and temporally restricted manner in the developing lens, limbs, kidney, teeth and testis (6, 7). In adult kidney, it is expressed in glomeruli and the peritubular vasculature, where VEGF-A is constitutively expressed (5, 8). It is thought to regulate delivery of VEGF-A by podocytes to the kidney endothelium (5).