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Rnd2 Uniquely Regulates Myelination by Oligodendrocytes Depending on Myelinating Process

63 Pages Posted: 1 Apr 2020 Publication Status: Under Review

See all articles by Yuki Miyamoto

Yuki Miyamoto

National Research Institute for Child Health and Development - Department of Pharmacology

Tomohiro Torii

Doshisha University

Miho Terao

National Research Institute for Child Health and Development

Shuji Takada

National Research Institute for Child Health and Development

Akito Tanoue

National Research Institute for Child Health and Development - Department of Pharmacology

Hironori Katoh

Kyoto University

Junji Yamauchi

National Research Institute for Child Health and Development - Department of Pharmacology

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Abstract

Oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around axons. While myelination is known to be one of the most dynamic cell morphological changes, the overall molecular pictures remain to be elucidated. Herein we describe the biphasic roles of Rnd2, an atypical branch of the Rho GTPase, in oligodendrocyte myelination during development and after maturation. Oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness in the onset of myelination whereas the knockout increased thickness in the subsequent process. Consistently, the biphasic role of Rnd2 is obtained using oligodendrocyte-specific Rnd2 transgenic mice. Indeed, Rho kinase and the substrate Mbs, the signaling unit regulating negatively myelination, exist in the decreased phosphorylated forms in the early developmental stage and in the increased phosphorylated forms in the subsequent stage. Therefore, Rnd2 uniquely regulates myelination, demonstrating the presence of a modulator that plays different roles depending on the myelination process.

Keywords: myelination; oligodendrocyte; biphasic; Rnd2; knockout; transgenic

Suggested Citation

Miyamoto, Yuki and Torii, Tomohiro and Terao, Miho and Takada, Shuji and Tanoue, Akito and Katoh, Hironori and Yamauchi, Junji, Rnd2 Uniquely Regulates Myelination by Oligodendrocytes Depending on Myelinating Process. Available at SSRN: https://ssrn.com/abstract=3564980 or http://dx.doi.org/10.2139/ssrn.3564980
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Yuki Miyamoto

National Research Institute for Child Health and Development - Department of Pharmacology ( email )

Japan

Tomohiro Torii

Doshisha University

Karasuma-Imadegawa Kamigyo
Kyoto 602-8580
Japan

Miho Terao

National Research Institute for Child Health and Development

Japan

Shuji Takada

National Research Institute for Child Health and Development

Japan

Akito Tanoue

National Research Institute for Child Health and Development - Department of Pharmacology

Japan

Hironori Katoh

Kyoto University

Yoshida-Honmachi
Sakyo-ku
Kyoto, 606-8501
Japan

Junji Yamauchi (Contact Author)

National Research Institute for Child Health and Development - Department of Pharmacology ( email )

Japan

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