CBLN1 is a 35kD secreted glycoprotein in the Cerebellin family of TNF superfamily molecules. Cerebellins contain an N-terminal collagenous domain and a C-terminal TNF/C1q-like domain. Mature human Cerebellin-1 shares 100% aa sequence identity with mouse and rat Cerebellin-1. It is expressed in the cerebellum, the parafascicular nucleus of the thalamus, and in the adrenal cortex and pancreatic islets. Cerebellin-1 forms noncovalent homotrimers that are disulfide-linked into hexamers. It can also form hetero-oligomers with Cerebellins-2, -3, and -4 and is required for the secretion of Cerebellin-3. Cerebellin-1 is subject to proteolysis which can liberate 15-mer or 16-mer bioactive peptides from the C1q domain or remove the regions necessaryfor trimer or hexamer formation. Formation of the hexamer is required for Cerebellin-1s ability to bind to synaptic structures. It binds to postsynaptic densities through direct interactions with the glutamate receptor subunit GluRd2 and to presynaptic membranes through direct interactions with alpha and beta Neurexins that contain the SS4 insert. The trans-synaptic trimolecular complex of GluRd2, Cerebellin-1, and Neurexin promotes both presynaptic and postsynaptic development. Cerebellin-1 itself is required for synaptic development, maintenance, and function. It can also be internalized by Purkinje cells following secretion by cerebellar granule cells. The 16-mer and 15-mer peptides derived from Cerebellin-1 exert multiple endocrine effects including promoting corticosteroid secretion by cortical adrenal cells, inhibiting glucose-stimulated insulin secretion from pancreatic islets, promoting Neuropeptide Y secretion by the hypothalamus, and decreasing plasma thyroid stimulating hormone (TSH) levels. Recombinant corresponding to human Cerebellin-1, Glu22-Leu193, with an N-terminal HA (YPYDVPDYA) tag, expressed in CHO cells. Swiss/Uniprot: P23435 Molecular Weight: ~20kD Biological Activity: Measured by its binding ability in a functional ELISA. When Recombinant Human Cerebellin-1 is coated at 5ug/ml, biotinylated recombinant rat NRXN-1 beta binds with an apparent KD < 0.5 nM. Measured by its ability to enhance neurite outgrowth of E16-E18 rat embryonic cortical neurons. Recombinant Human Cerebellin-1, immobilized at 3-30ug/mL, is able to significantly enhance neurite outgrowth. Storage and Stability: Lyophilized and reconstituted products are stable for 6 months after receipt at -20C. Reconstitute with sterile PBS. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
