Sasaki Binri, Oishi Momo, Aoki Tomoka, Hyodo Mai, Onchi Chinami, Yamada Nanako, Misawa Hitomi, Yamada Momona, Hayashi Chikako, Sekiguchi Kiyotoshi, Hamada Keisuke, Yamada Yuji, Kikkawa Yamato, Nomizu Motoyoshi, Suzuki Nobuharu
Department of Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo/Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, TMDU, Tokyo, Japan.
Glia. 2025 Aug;73(8):1692-1706. doi: 10.1002/glia.70027. Epub 2025 May 8.
In the central nervous system, oligodendrocytes (OLs) form myelin sheaths that accomplish the efficient transmission of nerve conduction for optimal motor and cognitive functions. OL development and differentiation are regulated by a variety of molecules, including extracellular matrix (ECM) proteins. ECM proteins are also useful as substrates for OL culture. However, the functions of ECM proteins in OL development and myelination remain unclear, and only a limited number of ECM proteins have been characterized and used in in vitro experiments. Here, we investigated the expression and function of laminin (LM) isoforms in OL differentiation and myelination. We found that LM α1, α2, and α4 chains were expressed around blood vessels at the stage of myelination in mice. Functional analyses using recombinant proteins of LM isoforms containing α1, α2, and α4 chains revealed that LM411 and LM411E8, the integrin binding domain of LM411, possessed significant activities in myelin membrane formation of OLs. Furthermore, the peptide A4G47 derived from LM411E8 promoted the activity, which provides evidence of the first peptide in OL myelin formation from ECM proteins. Our findings facilitate a better understanding of ECM functions in OL biology and the development of a new material in OL myelination.
在中枢神经系统中，少突胶质细胞（OLs）形成髓鞘，以实现神经传导的高效传递，从而实现最佳的运动和认知功能。OL的发育和分化受多种分子调控，包括细胞外基质（ECM）蛋白。ECM蛋白也可用作OL培养的底物。然而，ECM蛋白在OL发育和髓鞘形成中的功能仍不清楚，只有少数ECM蛋白已被鉴定并用于体外实验。在此，我们研究了层粘连蛋白（LM）异构体在OL分化和髓鞘形成中的表达和功能。我们发现，在小鼠髓鞘形成阶段，LMα1、α2和α4链在血管周围表达。使用含有α1、α2和α4链的LM异构体重组蛋白进行的功能分析表明，LM411及其整合素结合域LM411E8在OL的髓鞘膜形成中具有显著活性。此外，源自LM411E8的肽A4G47增强了该活性，这为ECM蛋白中首个参与OL髓鞘形成的肽提供了证据。我们的研究结果有助于更好地理解ECM在OL生物学中的功能，以及开发用于OL髓鞘形成的新材料。
