SCO-spondin
| SSPOP | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | SSPOP, SCO-spondin, SCO-spondin, pseudogene, SSPO | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 617356; MGI: 2674311; HomoloGene: 45453; GeneCards: SSPOP; OMA:SSPOP - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000197558 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029797 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c Gobron S, Monnerie H, Meiniel R, Creveaux I, Lehmann W, Lamalle D, et al. (May 1996). "SCO-spondin: a new member of the thrombospondin family secreted by the subcommissural organ is a candidate in the modulation of neuronal aggregation". Journal of Cell Science. 109 (5): 1053–1061. doi:10.1242/jcs.109.5.1053. PMID 8743952.
- ^ Meiniel A (March 2001). "SCO-spondin, a glycoprotein of the subcommissural organ/Reissner's fiber complex: evidence of a potent activity on neuronal development in primary cell cultures". Microscopy Research and Technique (in German). 52 (5): 484–495. doi:10.1002/1097-0029(20010301)52:5<484::AID-JEMT1034>3.0.CO;2-0. PMID 11241859.
- ^ a b Inada H, Corales LG, Osumi N (2023-03-07). "A novel feature of the ancient organ: A possible involvement of the subcommissural organ in neurogenic/gliogenic potential in the adult brain". Frontiers in Neuroscience. 17 1141913. doi:10.3389/fnins.2023.1141913. PMC 10027738. PMID 36960167.
- ^ a b c d e f g h i j k l m Sepúlveda V, Maurelia F, González M, Aguayo J, Caprile T (October 2021). "SCO-spondin, a giant matricellular protein that regulates cerebrospinal fluid activity". Fluids and Barriers of the CNS. 18 (1) 45. doi:10.1186/s12987-021-00277-w. PMC 8487547. PMID 34600566.
- ^ Corales LG, Inada H, Hiraoka K, Araki S, Yamanaka S, Kikkawa T, et al. (September 2022). "The subcommissural organ maintains features of neuroepithelial cells in the adult mouse". Journal of Anatomy. 241 (3): 820–830. doi:10.1111/joa.13709. PMC 9358730. PMID 35638289.
- ^ Schoebitz K, Garrido O, Heinrichs M, Speer L, Rodríguez EM (1986-01-01). "Ontogenetical development of the chick and duck subcommissural organ. An immunocytochemical study". Histochemistry. 84 (1): 31–40. doi:10.1007/BF00493417. PMID 2420757.
- ^ McDonald NQ, Hendrickson WA (May 1993). "A structural superfamily of growth factors containing a cystine knot motif". Cell. 73 (3): 421–424. doi:10.1016/0092-8674(93)90127-c. PMID 8490958.
- ^ Doliana R, Bot S, Bonaldo P, Colombatti A (November 2000). "EMI, a novel cysteine-rich domain of EMILINs and other extracellular proteins, interacts with the gC1q domains and participates in multimerization". FEBS Letters. 484 (2): 164–168. Bibcode:2000FEBSL.484..164D. doi:10.1016/S0014-5793(00)02140-2. PMID 11068053.
- ^ Amini R, Jain RP, Korzh V (2024-12-20). "Kcnb1-Kcng4 axis regulates Scospondin secretion and Reissner fiber development". bioRxiv 10.1101/2024.12.20.629661.
- ^ Nualart F, Cifuentes M, Ramírez E, Martínez F, Barahona MJ, Ferrada L, et al. (September 2023). "Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing". PLOS Biology. 21 (9) e3002308. doi:10.1371/journal.pbio.3002308. PMC 10513282. PMID 37733692.
Further reading
- Meiniel A, Meiniel R, Gonçalves-Mendes N, Creveaux I, Didier R, Dastugue B (2004). The Thrombospondin Type 1 Repeat (TSR) and Neuronal Differentiation: Roles of SCO-Spondin Oligopeptides on Neuronal Cell Types and Cell Lines∗. International Review of Cytology. Vol. 230. pp. 1–39. doi:10.1016/S0074-7696(03)30001-4. ISBN 978-0-12-364634-7. PMID 14692680.
- Meiniel O, Meiniel A (February 2007). "The complex multidomain organization of SCO-spondin protein is highly conserved in mammals". Brain Research Reviews. 53 (2): 321–327. doi:10.1016/j.brainresrev.2006.09.007. PMID 17126404. S2CID 7833761.
- Nakayama M, Kikuno R, Ohara O (November 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Research. 12 (11): 1773–1784. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
- Gonçalves-Mendes N, Simon-Chazottes D, Creveaux I, Meiniel A, Guénet JL, Meiniel R (July 2003). "Mouse SCO-spondin, a gene of the thrombospondin type 1 repeat (TSR) superfamily expressed in the brain". Gene. 312: 263–270. doi:10.1016/S0378-1119(03)00622-X. PMID 12909363.
- Gonçalves-Mendes N, Blanchon L, Meiniel A, Dastugue B, Sapin V (May 2004). "Placental expression of SCO-spondin during mouse and human development". Gene Expression Patterns. 4 (3): 309–314. doi:10.1016/j.modgep.2003.10.004. PMID 15053980.
- Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, et al. (May 2005). "Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution". Science. 308 (5725): 1149–1154. Bibcode:2005Sci...308.1149C. doi:10.1126/science.1108625. PMID 15790807. S2CID 13047538.