PMID- 29702083 OWN - NLM STAT- MEDLINE DCOM- 20190506 LR - 20190506 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1691 DP - 2018 Jul 15 TI - alphavbeta5 integrin mediates the effect of vitronectin on the initial stage of differentiation in mouse cerebellar granule cell precursors. PG - 94-104 LID - S0006-8993(18)30219-1 [pii] LID - 10.1016/j.brainres.2018.04.025 [doi] AB - Vitronectin (VN), one of the extracellular matrix proteins, controls the maturation of cerebellar granule cells (CGCs) through the promotion of the initial differentiation stage progress. However, the receptors of VN in the initial differentiation stage of CGC precursors (CGCPs) have not been clarified. In this study, we characterized the receptor candidates for VN in CGCPs. First, we confirmed that alphavbeta3 and alphavbeta5 integrins, which are receptor candidates for VN, were co-localized with VN in the developing cerebellum and primary cultured CGCPs. Next, the knockdown (KD) of alphav, beta3, and beta5 integrins with small interference RNA (siRNA) for each integrin reduced the ratio of Tuj1, a final differentiation marker, -positive CGCPs. We further studied whether alphavbeta3 and alphavbeta5 integrins control the initial differentiation stage. The KD of alphav and beta5, but not beta3, integrins significantly increased the ratio of transient axonal glycoprotein 1 (TAG1), an initial differentiation marker, -positive CGCPs, whereas the KD of alphav and beta3 integrins, not beta5 integrin, stimulated the proliferation of CGCPs. Overexpression of beta5 integrin stimulated the progress of the initial differentiation stage as well. To confirm the interaction between alphavbeta5 integrin and VN, VN was added to beta5 integrin-KD CGCPs. The promotion of the progress of initial differentiation by VN was abrogated by beta5 integrin KD using small hairpin RNA (shRNA). Taken together, our results indicated that alphavbeta5 integrin, as the very receptor of VN, is responsible for the progress of the initial differentiation stage in mouse CGCPs. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Abe, Ayaka AU - Abe A AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Hashimoto, Kei AU - Hashimoto K AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan; Japan Society for the Promotion of Science, Kojimachi, Chiyoda-ku, Tokyo, Japan. FAU - Akiyama, Ayumi AU - Akiyama A AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Iida, Momoe AU - Iida M AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Ikeda, Natsumi AU - Ikeda N AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Hamano, Ayana AU - Hamano A AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Watanabe, Riho AU - Watanabe R AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. FAU - Hayashi, Yokichi AU - Hayashi Y AD - Department of Life Science, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Miyamoto, Yasunori AU - Miyamoto Y AD - Graduate School of Humanities and Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan. Electronic address: miyamoto.yasunori@ocha.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180424 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Contactin 2) RN - 0 (Integrin alphaVbeta3) RN - 0 (Ki-67 Antigen) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Vitronectin) RN - 0 (Tubulin) RN - 0 (Vitronectin) RN - 0 (beta3 tubulin, mouse) RN - 0 (integrin alphaVbeta5) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) SB - IM MH - Age Factors MH - Animals MH - Animals, Newborn MH - Cell Differentiation/genetics MH - Cell Proliferation/genetics MH - Cells, Cultured MH - Cerebellum/*cytology/growth & development MH - Contactin 2/metabolism MH - Gene Expression Regulation, Developmental/*physiology MH - Integrin alphaVbeta3/genetics/metabolism MH - Ki-67 Antigen/metabolism MH - Mice MH - Mice, Inbred ICR MH - Neural Stem Cells/*physiology MH - Organ Culture Techniques MH - Phosphopyruvate Hydratase/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - Receptors, Vitronectin/*genetics/*metabolism MH - Tubulin/metabolism MH - Vitronectin/metabolism OTO - NOTNLM OT - Cerebellar granule cell OT - Differentiation OT - Vitronectin OT - alphavbeta3 integrin OT - alphavbeta5 integrin EDAT- 2018/04/28 06:00 MHDA- 2019/05/07 06:00 CRDT- 2018/04/28 06:00 PHST- 2017/08/25 00:00 [received] PHST- 2018/03/29 00:00 [revised] PHST- 2018/04/20 00:00 [accepted] PHST- 2018/04/28 06:00 [pubmed] PHST- 2019/05/07 06:00 [medline] PHST- 2018/04/28 06:00 [entrez] AID - S0006-8993(18)30219-1 [pii] AID - 10.1016/j.brainres.2018.04.025 [doi] PST - ppublish SO - Brain Res. 2018 Jul 15;1691:94-104. doi: 10.1016/j.brainres.2018.04.025. Epub 2018 Apr 24.