1: Regulation of RhoA by STAT3 coordinates glial scar formation
Science of the Month - October 2017
JOURNAL OF CELL BIOLOGY
Renault-Mihara Francois, Mukaino Masahiko, Shinozaki Munehisa, Kumamaru Hiromi, Kawase Satoshi, Baudoux Matthieu, Ishibashi Toshiki, Kawabata Soya, Nishiyama Yuichiro, Sugai Keiko, Yasutake Kaori, Okada Seiji, Nakamura Masaya, Okano Hideyuki
When an injury occurs in the central nervous system, reactive astrocytes in the surrounding area form a glial scar. For this reason, reactive astrocytes have traditionally been considered detrimental, but in the subacute phase of spinal cord injury, they play a beneficial role by limiting tissue damage and inflammation, thereby preserving remaining spinal cord function. We had previously found that STAT3 signaling in reactive astrocytes is necessary for proper glial scar formation after spinal cord injury (Okada et al., Nat Med, 2006), but the underlying molecular mechanism was unknown. In this study, we revealed in vitro that STAT3 regulates reactive astrocytes via the small G protein RhoA. Specifically, we found that actomyosin tension, adhesion remodeling with the extracellular matrix, and cell migration are regulated. We also discovered that the STAT3/RhoA pathway plays a crucial role in glial scar formation in vivo and that the abnormalities in reactive astrocyte dynamics and glial scar formation caused by STAT3 deletion can be normalized by suppressing PTEN expression. In future research, we hope to clarify whether the novel downstream molecular mechanism of STAT3 discovered in this study is involved in the key functions of normal astrocytes, such as glutamate clearance, potassium ion homeostasis, and the regulation of synaptic transmission and plasticity.
(Hideyuki Okano, Department of Physiology, 62nd Graduating Class)
2: The C1q complement family of synaptic organizers: not just complementary
In our brains, countless neurons connect via synapses to form neural networks. In recent years, many psychiatric and neurological disorders and developmental disabilities, such as Alzheimer's disease, schizophrenia, and autism spectrum disorder, are increasingly considered to be "synaptopathies" caused by synaptic dysfunction. Therefore, elucidating how synapses are formed, maintained, and lost in pathological processes is a critical issue. Recently, our group pioneered the discovery of the C1q family, a new group of synapse-organizing molecules (Nature Neurosci, '05; Neuron, '15; Science '10, Science '16). The C1q family is a series of molecules similar to the complement C1q of the innate immune system, and members like Cbln and C1qL regulate synapse formation in various brain regions. It has also been recently reported that in Alzheimer's disease and schizophrenia, the complement C1q itself is involved in the process of synapse elimination. In this review, we summarize and discuss the findings to date on the mechanisms of synaptic regulation by C1q family molecules. It is hoped that regulating C1q family molecules will lead to new therapeutic methods for psychiatric and neurological disorders.
(Michisuke Yuzaki, Department of Physiology, equivalent to the 64th Graduating Class)