SCO-spondin

Last updated

SSPOP
Identifiers
Aliases SSPOP , SCO-spondin, SCO-spondin, pseudogene, SSPO
External IDs OMIM: 617356; MGI: 2674311; HomoloGene: 45453; GeneCards: SSPOP; OMA:SSPOP - orthologs
Orthologs
SpeciesHumanMouse
Entrez

23145

243369

Ensembl

ENSG00000197558

ENSMUSG00000029797

UniProt

A2VEC9

Q8CG65

RefSeq (mRNA)

NM_198455

NM_173428

RefSeq (protein)

NP_940857

NP_775604

Location (UCSC) Chr 7: 149.78 – 149.83 Mb Chr 6: 48.43 – 48.48 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000197558 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029797 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 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.
  6. ↑ 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.
  7. 1 2 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.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Amini R, Jain RP, Korzh V (2024-12-20). "Kcnb1-Kcng4 axis regulates Scospondin secretion and Reissner fiber development". bioRxiv. doi:10.1101/2024.12.20.629661 . Retrieved 2025-12-02.
  14. ↑ 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.

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