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Investigating the Role of Human Perlecan Domain V in Promoting Neurite Outgrowth

This study explores the function of perlecan in the basement membrane and its impact on neurite growth. Research demonstrates that specific fragments of human perlecan promote neurite outgrowth and interact with acetylcholinesterase. The results suggest a potential mechanism for promoting neurite growth.

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Investigating the Role of Human Perlecan Domain V in Promoting Neurite Outgrowth

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  1. 探討人類珍珠素蛋白多醣第五片段促進神經纖維生長之作用 基底膜(basement membrane, BM)是由第四型膠原蛋白(type IV collagen)、層黏蛋 白(laminin)及蛋白多醣(proteoglycan)等物質所構成，主要功能是扮演維持上皮及內皮細胞型態與細胞附著及做為細胞生長支架(scaffold)的功能。硫酸肝素蛋白多醣(HSPG)為BM中重要的蛋白多醣類。先前研究指出HSPG具有促進神經纖維生長的功能，而珍珠素(perlecan)即屬於HSPG的一種，本研究是在探討基底膜中硫酸肝素蛋白多醣(heparan sulfate proteoglycan)珍珠素(perlecan)在神經系統所扮演的角色與功能，先前的研究中證實重組的人類珍珠素蛋白多醣第五片段(human perlecan domain V; H.Pln DV)在以laminin為基材貼覆的環境下具有促進背根神經節神經纖維生長的能力，因此本實驗主要目的是以重組基因技術(recombinant DNA technology)將perlecan domain V分成兩個含類似組成的片段(H.Pln DV-I, H.Pln DV-II)探討其對神經纖維生長之影響及作用機轉，研究結果顯示兩片段都會促進神經纖維的生長，先前文獻中顯示perlecan會與乙醯膽鹼酯酵素(AchE)有交互作用且AchE有促進神經纖維生長之作用，本研究第二部分探討perlecan與AchE的作用是否是透過perlecan domain V。結果顯示H.Pln DV, DV-I, DV-II可直接與AchE結合。推測H.Pln DV可能藉由與AchE的結合促進神經纖維的生長的。

  2. Studies of the effect of human perlecan domain V on promoting neurite outgrowth • The major components of basement membrane (BM) are type IV collagen, laminin and proteoglycans. The basement membrane fuctions as a scaffold to maintain the morphology of epithelium and endothelial cells. The major type of proteoglycan in BM is heparan sulfate proteoglycan (HSPG). Previous study has shown that HSPG can promote the neurite outgrowth. Our studies are to understand the role of perlecan, which is the predominant HSPG in BM in the neurite outgrowth. Our previous study showed that recomibnant human perlecan domain V could promote the neurite outgrowth of dorsal root ganglion (DRG) neurons in laminin coating. Here we divided the perlecan domain V (H.Pln DV) into two smaller fragment to identify the minimum fragment required for promoting the neurite outgrowth. The result showed that both of these two smaller fragments derived from perlecan domain V could promote the neurite outgrowth of DRG neurons. Previously study showed that perlecan and acetylcholinesterase (AchE) could interact with each other and AchE could promote the neurite outgrowth. Our further studies showed that H.Pln DV, H.Pln DV-I, H.Pln DV-II could bind to AchE. It suggests that H.Pln DV promoting the neurite outgrowth may be mediated by binding to AchE.

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