Tetraspanin(Tspan)は4回膜貫通ドメインと2つの細胞外ループを持つ膜タンパク質であり, Tspanを介して様々な膜タンパク質が細胞膜上に集合し, 膜タンパク質の輸送やシグナル伝達を調節している。我々は, 網膜で発現している新規のTspanを見出し, 生後6日目のマウス網膜においてTspan18が動静脈および神経節細胞で発現していること, Tspan18lacZ/lacZマウスではコントロールマウスよりも網膜血管の伸びが悪く, 動静脈の本数が減少していることを見出した。Tspan18の結合候補因子を同定し, この因子のシグナル伝達をTspan18が調節していることが示唆された。
Tetraspanins (Tspans) are membrane-anchored molecules with 4 transmembrane regions, which promote clustering of other membranous proteins by forming "tetraspanin-enriched microdomain". Integrins and Immunoglobulin superfamily proteins have been identified as their binding proteins, and thus Tspans are thought to modulate the signal transduction associated with these molecules. However, the function of tetraspanins in vascular development has not been understood well. Here, we found some Tspans are expressed in endothelial cells, especially those in mature (arterial and venous) vessels. Conventional or endothelial-specific knockout of Tspan showed a significant reduction in the number of arterioles and venules and reduced radial vascular growth. In vitro data suggest that Tspan directly interacts with other membrane proteins involved in angiogenesis. Overall, Tspan might regulate the formation of arterioles and venules by clustering other membrane proteins.
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