Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas. Issue 2 (29th January 2019)

• Record Type: Journal Article
• Authors: Shimizu, Takeshi; Osanai, Yasuyuki; Tanaka, Kenji F.; Thai, Truc Quynh; Abe, Manabu; Natsume, Rie; Sakimura, Kenji; Ikenaka, Kazuhiro
• Is Part Of: Journal of neurochemistry. Volume 150:Issue 2(2019)
• Page Start: 158
• Page End: 172
• Publication Date: 2019-01-29
• Subjects: mechanical stress -- mechanosensor -- oligodendrocyte -- p130Cas; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14657
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimulation can be transduced into intracellular biochemical signals through mechanosensors, such as integrin, p130Cas, talin and vinculin. However, the molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that morphology of OL was affected by knockdown of the mechanosensors p130Cas or talin1. Stretching of OL precursor cells induced the phosphorylation of p130Cas and talin‐associated assembly of vinculin. Shear stress decreased the number of OL processes, whereas these effects were mechanically suppressed by dominant‐negative (DN) p130Cas, but not by DN‐talin1. To investigate the roles of p130Cas in post‐natal OLs in vivo, we constructed a novel p130Cas knock‐in mouse and found overexpression of p130Cas in vivo affected the number of mature OLs in the cortex. These results indicate that the mechanosensor p130Cas controls both OL morphogenesis and maturation. Abstract : Oligodendrocytes (OLs) are influenced by two types of mechanical forces: intracellularly generated traction forces and extracellularly applied forces caused by surrounding microenvironments. We found that a mechanosensor p130Cas sensed these mechanical forces and controlled the OL morphology. We constructed a novel p130Cas knock‐in mouse and found that overexpression of p130Cas in vivo affected the number of mature OLs in the cortex. These results indicate that OLs are sensitive to mechanical stresses, which impact on OL morphogenesis and maturation.