SCO-spondin
From Wikipedia, the free encyclopedia
SCO-Spondin is a large protein that exists in most chordates and is encoded in humans by the SSPO gene.[5] SCO-Spondin is a glycoprotein which is over 550 kDa in size. SCO-Spondin is a matricellular protein, secreted by the subcommissural organ (SCO) located beneath the posterior commissure located at the entrance of the Sylvian aqueduct,[6][7] into the cerebrospinal fluid (CSF). SCO-spondin has the binding features of an LDL-binding protein.[8] SCO-spondin has been characterized in zebrafish, mouse,[9] and birds.[10]
| SSPOP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | SSPOP, SCO-spondin, SCO-spondin, pseudogene, SSPO | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 617356; MGI: 2674311; GeneCards: SSPOP | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Functions
SCO-spondin's function is incompletely characterized, but is believed to be involved in formation of Reissner's fibers (RF). This process involves a continuous deposition, aggregation and disaggregation of the SCO-spondin along the RF length.[8]
Early in development, SCO-spondin also plays a role in modulation of neural differentiation.[8] 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.[7] It has been observed in the fetal and infancy stages of humans.[8]
Domains and structure
SCO-spondin contains dozens of tandem domains, including thrombospondin-like repeat (TSR), vWF-C, EGF-like, and LDL receptor A. It also includes an elastin microfibril interface (EMI) domain at the N-terminus and a C-terminal cystine knot (CTCK) domain at the C-terminus.[8]
The TSR domains, found in many matricelluar proteins, function in cell attachment, protein to protein interactions, and protein-glycoaminoglycan interactions.[8] There are many molecules that can interact with this domain including FGF-2.[8] The vWF-C domain is a 'chordin like cysteine rich repeat', which plays a role in regulating TGF-β and other proteins.[8] The CTCK domain is responsible for cell adhesion[11] and protein-protein interactions, possibly suggesting a role of SCO-spondin in forming intermolecular aggregates with other CSF proteins containing this domain.[8] The EGF-like domains are thought to associate with integrins and cell-surface receptors such as the EGF receptor,[8] 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.[8]
In addition to these domains, SCO-spondin contains an EMI domain, thought to enable multimer formation by disulfide bonding,[12][8] 12 or more trypsin inhibitor-like (TIL) domains, and multiple vWF-D domains. These latter domains are thought to be involved in formation of intermolecular networks with other CSF proteins.[8]
In zebrafish,[13] the voltage gated potassium channel Kv2.1 can regulate the assembly of SCO-spondin and its bundling into the Reissner fibers.
History
SCO-spondin was first discovered in 1996[5] and then was later sequenced in 2000. [5] In humans, the gene that codes for SCO-spondin, SSPO or SSPOP, is classified as a pseudogene, not encoding a working protein. However, irregular SCO-spondin expression has been identified in humans and the protein's secretion has been linked to various disease states.[14]