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Extracellular neuroleukin enhances neuroleukin secretion from astrocytes and promotes axonal growth
細胞外ニューロロイキンはアストロサイトからのニューロロイキン分泌を促し、神経細胞の軸索伸展を促す
Tanie Toshitaka（谷江 良崇），田辺 紀生，久保山 友晴，東田 千尋
Division of Neuromedical Science, Department of Bioscience, Institute of Natural Medicine, University of Toyama
Under pathological conditions in the central nervous system (CNS), such as traumatic injury, astrocytes show detrimental effects, against neurons. It is also known that astrocytes sometimes exert beneficial effects, for example, neuroprotection and secretion of axonal growth factors. If it is possible to promote beneficial effects of astrocytes after injury, dysfunctions of the injured CNS might be improved. However, a way of promotion of beneficial functions in astrocytes has not been elucidated. In this study, we focused on Neuroleukin (NLK) that was known to have axonal growth activities in neurons. Although it was reported that NLK was secreted from astrocytes, the function of NLK in astrocytes is rarely understood. Therefore, we aimed to clarify the functional significance of secreted NLK from astrocytes and the mechanism of NLK secretion in astrocytes. Stimulation of cultured astrocytes with recombinant NLK significantly elevated the secretion of NLK from astrocytes. Furthermore, astrocyte conditioned medium treated with NLK increased the axonal density in cultured cortical neurons. Recombinant NLK itself directly increased the axonal density in cultured neurons. These results indicated that NLK is an axonal growth factor secreted from astrocytes, and secretion of NLK from astrocytes is stimulated by extracellular NLK. In addition, 78 kDa glucose regulated protein (GRP78) was suggested as a receptor for NLK, relating to NLK secretion from astrocytes. When NLK was injected to the lesion site in spinal cord injured mice, axonal density in the injured region was significantly increased and hindlimb motor function was also improved. These results suggest that NLK-GRP78 signaling is important for beneficial effects of astrocytes. | | WD1-2
High temperature region in growth cones heats up TRPV2-mechanosensor function and axonal outgrowth
膜伸展刺激感知センサー・TRPV2チャネルによる熱を介した神経回路形成の制御
Oda Mai（織田 麻衣）1，杉尾 翔太1，岩田 裕子2，岡部 弘基3，小野 勝彦4，石崎 泰樹1，柴崎 貢志1
1Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine
2Department of Clinical Research and Development, National Cerebral and Cardiovascular Center Research Institute
3Graduate School of Pharmaceutical Sciences, The University of Tokyo
4Department of Biology, Kyoto Prefectural University of Medicine
We previously reported that TRPV2 is a mechanosensor channel which contributes to axonal outgrowth in membrane stretch dependent manner (J. Neurosci. 2010, JPS 2016, FASEB J. 2017), although TRPV2 was originally cloned as a noxious heat sensor (>52°C). These results indicate that TRPV2 is an important component for the responses against the stretch. In this study, we examined the intracellular temperature distribution during axonal outgrowth by a temperature-imaging method. We found that specific high temperature regions (2-4°C higher) were occasionally localized in the growth cones. We hypothesized that the higher temperature might accelerate the sensitivity of TRPV2 for mechanical stimuli. Hence, we evaluated the mechanical stimuli-evoked TRPV2 currents at various temperatures by a whole cell patch-clamp recording. Surprisingly, physiological temperature (37°C) was insufficient to sensitize the TRPV2 activation. Unexpectedly, over 39°C condition dramatically accelerates the TRPV2 sensitivity for mechanical stimuli. These results suggest that the hot spots in growth cones contribute to accelerate axonal outgrowth through the TRPV2 sensitization. We compared the axonal outgrowth at 37°C or 39°C culture conditions, and found that the 39°C condition had significantly longer axons compared with 37°C condition through the TRPV2 activation. To examine specific in vivo roles of TRPV2, we generated motor/sensory neuron-specific TRPV2 CKO mice, and analyzed their specific defects. We found that TRPV2 CKO mice had abnormal peripheral axons in embryonic primordial fingers. Taken together, the mechanosensor function of TRPV2 is sensitized by high temperature region (2-4°C higher) generated by growth cone movements, and is necessary to form long peripheral axons in embryos. |
