Reactome | Tenascins C, R, (X, N) bind lecticans

Tenascins C, R, (X, N) bind lecticans

Stable Identifier

R-HSA-2424246

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Tenascins are a family of 4 oligomeric extracellular glycoproteins, tenascin (TN) C, R, X, and N (also called W). In rotary shadowing images TNC is seen as a symmetrical structure called a hexabrachion (Erickson & Iglesias 1984). This hexamer is formed from initial trimers (Kammerer et al. 1988). All members of the family are believed able to form trimers but only C, R and W have the extra cysteine required for form hexamers. All have amino-terminal heptad repeats, epidermal growth factor (EGF)-like repeats, fibronectin type III domain repeats, and a carboxyl-terminal fibrinogen-like globular domain (Hsia & Schwartzbauer 2005). TNC was the first family member to be discovered and is the best characterised. Its subunits vary greatly in size (between 190 and 330 kDa of the tenascin-C monomer) due to glycosylation and splicing isoforms (Joester & Faissner 1999). During embryonic development TNC is expressed in neural, skeletal, and vascular tissues. In adults it is detectable only in tendon and tissues undergoing remodeling processes such as wound repair and neovascularization, or in pathological processes such as inflammation and tumorigenesis (Midwood & Orend 2009). TNR forms dimers and trimers (Norenberg et al. 1992) and is expressed only in the developing and adult central nervous system. TNC and TNR-null mice (single and double knock-outs) have surprisingly normal gross phenotypes, but exhibit behavioural and wound healing abnormalities (Mackie & Tucker 1999, Montag-Sallaz & Montag 2003). TNX is the largest member of the family and is widely expressed during development, but in adults is limited to musculoskeletal, cardiac, and dermal tissue. It can form trimers, though it lacks the amino-terminal cysteine residues involved in hexamer formation. It is clearly associated with a variant of a heritable connective tissue disorder known as Ehler-Danlos Syndrome, which is associated with fibrillar collagen defects (Burch et al. 1997, Mao et al. 2002). TNY is thought to be an avian orthologue of TNX (Chiquet-Ehrismann 2004). TNN, first identified in zebrafish (Weber et al. 1998), is the least well characterized member of the tenascin family. It forms hexamers (Degen et al. 2007) and is expressed in developing skeletal tissue and neural crest cells, a pattern that partially overlaps with TNC.

TNC and TNR bind to members of the lectican family, a class of extracellular chondroitin sulfate proteoglycans consisting of aggrecan, versican, brevican and neurocan. TNC binds aggrecan (Lundell et al. 2004), versican (Tsujii et al. 2006) and neurocan (Milev et al. 1994, Grumet et al. 1994, Rauch et al. 1997). TNR binds aggrecan (Aspberg et al. 1997, Lundell et al. 2004), versican (Aspberg et al. 1995, 1997), brevican Aspberg et al. 1997, Hagihara et al. 1999) and neurocan (Aspberg et al. 1997).

Literature References

PubMed ID	Title	Journal	Year
9341124	Mapping of a defined neurocan binding site to distinct domains of tenascin-C Fröhlich, L, Retzler, C, Göhring, W, Fässler, R, Clement, A, Rauch, U, Faissner, A	J. Biol. Chem.	1997
16493581	Involvement of tenascin-C and PG-M/versican in flexor tenosynovial pathology of idiopathic carpal tunnel syndrome Yoshida, T, Tsujii, M, Uchida, A, Morita, A, Hirata, H, Imanaka-Yoshida, K	Histol. Histopathol.	2006
15296743	Structural basis for interactions between tenascins and lectican C-type lectin domains: evidence for a crosslinking role for tenascins al-Karadaghi, S, Olin, AI, Lundell, A, Mörgelin, M, Logan, DT, Aspberg, A	Structure	2004
9294172	The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety Shimonaka, M, Miura, R, Heinegârd, D, Bourdoulous, S, Schachner, M, Aspberg, A, Ruoslahti, E, Yamaguchi, Y	Proc. Natl. Acad. Sci. U.S.A.	1997