PMID- 33444672
OWN - NLM
STAT- MEDLINE
DCOM- 20210429
LR  - 20210429
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 746
DP  - 2021 Feb 16
TI  - Vitronectin regulates the axon specification of mouse cerebellar granule cell 
      precursors via alphavbeta5 integrin in the differentiation stage.
PG  - 135648
LID - S0304-3940(21)00026-4 [pii]
LID - 10.1016/j.neulet.2021.135648 [doi]
AB  - Vitronectin, an extracellular matrix protein, controls the differentiation of 
      cerebellar granule cell precursors (CGCPs) via alphavbeta5 integrin, particularly in the 
      initial stage of differentiation to granule cells. In this study, we determined 
      whether vitronectin regulates axon specification in this initial differentiation 
      stage of CGCPs. First, we analyzed whether vitronectin deficiency, beta5 integrin 
      knockdown (KD), and beta5 integrin overexpression affect axon specification of 
      primary cultured CGCPs. Vitronectin deficiency and beta5 integrin KD inhibited axon 
      formation, while vitronectin administrated- and beta5 integrin overexpressed-neurons 
      formed multiple axons. Moreover, KD of beta5 integrin suppressed vitronectin-induced 
      multiple axon formation. These findings indicate that vitronectin contributes to 
      regulating axon specification via alphavbeta5 integrin in CGCPs. Next, we determined the 
      signaling pathway involved in regulating vitronectin-induced axon specification. 
      Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited 
      vitronectin-induced multiple axon specification, and lithium chloride, an 
      inhibitor of glyocogen synthase kinase 3 beta (GSK3beta), attenuated the inhibitory 
      effect of vitronectin-KO and beta5 integrin KD on the specification of CGCPs. In 
      addition, vitronectin induced the phosphorylation of protein kinase B (Akt) and 
      GSK3beta in neuroblastoma Neuro2a cells. Taken together, our results indicate that 
      vitronectin plays an important factor in axon formation process in CGCPs via a beta5 
      integrin/PI3K/GSK3beta pathway.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Oishi, Yuko
AU  - Oishi Y
AD  - Graduate School of Humanities and Sciences, 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, Otsuka, Bunkyo-ku, Tokyo, Japan; 
      Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, 
      Tokyo, Japan.
FAU - Abe, Ayaka
AU  - Abe A
AD  - Graduate School of Humanities and Sciences, Otsuka, Bunkyo-ku, Tokyo, Japan; 
      Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, 
      Tokyo, Japan.
FAU - Kuroda, Maho
AU  - Kuroda M
AD  - Graduate School of Humanities and Sciences, Otsuka, Bunkyo-ku, Tokyo, Japan; 
      Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, 
      Tokyo, Japan.
FAU - Fujii, Ai
AU  - Fujii A
AD  - Graduate School of Humanities and Sciences, Otsuka, Bunkyo-ku, Tokyo, Japan; 
      Institute for Human Life Innovation, Ochanomizu University, Otsuka, Bunkyo-ku, 
      Tokyo, Japan.
FAU - Miyamoto, Yasunori
AU  - Miyamoto Y
AD  - Graduate School of Humanities and Sciences, 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 - 20210111
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Vitronectin)
RN  - 0 (integrin alphaVbeta5)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/*metabolism
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cells, Cultured
MH  - Cerebellum/cytology/drug effects/*metabolism
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neural Stem Cells/drug effects/*metabolism
MH  - Pregnancy
MH  - Receptors, Vitronectin/*metabolism
MH  - Vitronectin/*metabolism/pharmacology
OTO - NOTNLM
OT  - Axon specification
OT  - Cerebellar granule cell
OT  - GSK3
OT  - Integrin
OT  - PI3K
OT  - Vitronectin
EDAT- 2021/01/15 06:00
MHDA- 2021/04/30 06:00
CRDT- 2021/01/14 20:11
PHST- 2020/02/05 00:00 [received]
PHST- 2020/12/12 00:00 [revised]
PHST- 2021/01/06 00:00 [accepted]
PHST- 2021/01/15 06:00 [pubmed]
PHST- 2021/04/30 06:00 [medline]
PHST- 2021/01/14 20:11 [entrez]
AID - S0304-3940(21)00026-4 [pii]
AID - 10.1016/j.neulet.2021.135648 [doi]
PST - ppublish
SO  - Neurosci Lett. 2021 Feb 16;746:135648. doi: 10.1016/j.neulet.2021.135648. Epub 
      2021 Jan 11.