Testican‐3: a brain‐specific proteoglycan member of the BM‐40/SPARC/osteonectin family

Abstract

The testicans are a three-member family of secreted proteoglycans structurally related to the BM-40/secreted protein acidic and rich in cystein (SPARC) osteonectin family of extracellular calcium-binding proteins. In vitro studies have indicated that testicans are involved in the regulation of extracellular protease cascades and in neuronal function. Here, we describe the biochemical characterization and tissue distribution of mouse testican-3 as well as the inactivation of the corresponding gene. The expression of testican-3 in adult mice is restricted to the brain, where it is located diffusely within the extracellular matrix, as well as associated with cells. Brain-derived testican-3 is a heparan sulphate proteoglycan.In cell culture, the core protein is detected in the supernatant and the extracellular matrix, whereas the proteoglycan form is restricted to the supernatant. This indicates possible interactions of the testican-3 core protein with components of the extracellular matrix which are blocked by addition of the glycosaminoglycan chains. Mice deficient in testican-3 are viable and fertile and do not show an obvious phenotype. This points to a functional redundancy among the different members of the testican family or between testican-3 and other brain heparan sulphate proteoglycans. 1998]. Their modular structure is characterized by an N-terminal testican-specific domain followed by the follistatin-like (FS) and extracellular calciumbinding (EC) domains characteristic of the BM-40 family. Towards the C-terminus they contain a thyroglobulin-like domain (TY) and a novel sequence (domain V), which includes two potential glycosaminoglycan attachment sites.Testican-1 was originally isolated as a proteolytic fragment from human seminal plasma carrying chondroitin sulphate and heparan sulphate chains (Bonnet et al. 1993). In the mouse, testican-1 is predominantly expressed in the nervous system during embryonic development and its expression correlates with periods of neuronal migration and axonal growth (Charbonnier et al. 2000). In adult mice, expression is restricted to the brain where it is located at post-synaptic densities (Bonnet et al. 1996). In search for homologous members of the BM-40 family, we identified cDNAs that were most similar to testican-1 and designated the corresponding proteins testican-2 and -3 (Vannahme et al. 1999;Hartmann and Maurer 2001).In adult mice, testican-2 shows a broader tissue distribution than testican-1. Although the proteoglycan can be found

Structural Abnormalities of Corpus Callosum and Cortical Axonal Tracts Accompanied by Decreased Anxiety-Like Behavior and Lowered Sociability in Spock3-Mutant Mice

“…Consistent with this notion, no obvious phenotypes have been observed in the single Spock1 or Spock3 knockout mice [6,9]. On the other hand, SPOCK1 carries both heparan and chondroitin sulfate chains [6], whereas SPOCK2 and 3 are pure heparan sulfate proteoglycans, although SPOCK2 is N-glycosylated and SPOCK3 carries several mucin-type O-glycans [6,7], suggesting that there might be different physiological roles specific to each SPOCK. Indeed, in cultured cells, SPOCK1 and SPOCK3 are able to modulate pro-matrix metalloproteinase processing via the negative regulation of its activator, the membrane-type matrix metalloproteinase, while SPOCK2 abrogates this modulation [10,11].…”

“…SPOCKs contain an N-terminal unique domain, a follistatin-like domain, extracellular calcium-binding domains characteristic of the BM-40 family, a thyroglobulin-like domain, and a C-terminal domain including two potential glycosaminoglycan attachment sites (fig. 1a) [6,7]. All three members are expressed mainly in the brain in similar profiles [6,7,8], leading to the notion that they may be functionally redundant.…”

“…1a) [6,7]. All three members are expressed mainly in the brain in similar profiles [6,7,8], leading to the notion that they may be functionally redundant. Consistent with this notion, no obvious phenotypes have been observed in the single Spock1 or Spock3 knockout mice [6,9].…”

“…All three members are expressed mainly in the brain in similar profiles [6,7,8], leading to the notion that they may be functionally redundant. Consistent with this notion, no obvious phenotypes have been observed in the single Spock1 or Spock3 knockout mice [6,9]. On the other hand, SPOCK1 carries both heparan and chondroitin sulfate chains [6], whereas SPOCK2 and 3 are pure heparan sulfate proteoglycans, although SPOCK2 is N-glycosylated and SPOCK3 carries several mucin-type O-glycans [6,7], suggesting that there might be different physiological roles specific to each SPOCK.…”

“…SPOCKs/TESTICANs (hereafter called ‘SPOCKs' according to public genome databases) are a family of proteoglycans that are expressed mainly in the brain and constitute a subgroup within the BM-40/SPARC/osteonectin family of modular extracellular proteins [5,6]. SPOCKs contain an N-terminal unique domain, a follistatin-like domain, extracellular calcium-binding domains characteristic of the BM-40 family, a thyroglobulin-like domain, and a C-terminal domain including two potential glycosaminoglycan attachment sites (fig.…”