Cerebellin-1: Proteins and Enzymes

Cerebellin-1 (CBLN1) is a 35 kDa 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. Cerebellin-1 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. Cerebellin-1 binds to postsynaptic densities through direct interactions with the glutamate receptor subunit GluR delta 2 and to presynaptic membranes through direct interactions with alpha and beta Neurexins that contain the SS4 insert. The trans-synaptic trimolecular complex of GluR delta 2, Cerebellin-1, and Neurexin promotes both presynaptic and postsynaptic development. Peptides derived from Cerebellin-1 proteolysis 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.