SCO-spondin
SCO-Spondin is a large protein that exists in most chordates and is encoded in humans by the SSPO gene. SCO-Spondin is a glycoprotein which is over 550 kDa in size. SCO-Spondin is a matricellular protein, secreted by the subcommissural organ located beneath the posterior commissure located at the entrance of the Sylvian aqueduct, into the cerebrospinal fluid. SCO-spondin has the binding features of an LDL-binding protein. SCO-spondin has been characterized in zebrafish, mouse, and birds.
Functions
SCO-spondin's function is incompletely characterized, but is believed to be involved in formation of Reissner's fibers. This process involves a continuous deposition, aggregation and disaggregation of the SCO-spondin along the RF length.Early in development, SCO-spondin also plays a role in modulation of neural differentiation. The secretion of SCO-spondin influences the rate of RF growth, which varies considerably between species.
Human SCO-spondin is poorly researched, and any role in adult human brains remains unknown. It has been observed in the fetal and infancy stages of humans.
Domains and structure
SCO-spondin contains dozens of tandem domains, including thrombospondin-like repeat, vWF-C, EGF-like, and LDL receptor A. It also includes an elastin microfibril interface domain at the N-terminus and a C-terminal cystine knot domain at the C-terminus.The TSR domains, found in many matricelluar proteins, function in cell attachment, protein to protein interactions, and protein-glycoaminoglycan interactions. There are many molecules that can interact with this domain including FGF-2. The vWF-C domain is a 'chordin like cysteine rich repeat', which plays a role in regulating TGF-β and other proteins. The CTCK domain is responsible for cell adhesion and protein-protein interactions, possibly suggesting a role of SCO-spondin in forming intermolecular aggregates with other CSF proteins containing this domain. The EGF-like domains are thought to associate with integrins and cell-surface receptors such as the EGF receptor, and the LDL-r A domains are thought to bind to the same binding partners as the LDL receptor, including low-density lipoprotein, amyloid-β, reelin, and clusterin, all of which can be found in the CSF under some conditions.
In addition to these domains, SCO-spondin contains an EMI domain, thought to enable multimer formation by disulfide bonding, 12 or more trypsin inhibitor-like domains, and multiple vWF-D domains. These latter domains are thought to be involved in formation of intermolecular networks with other CSF proteins.
In zebrafish, the voltage gated potassium channel Kv2.1 can regulate the assembly of SCO-spondin and its bundling into the Reissner fibers.