論文

査読有り 筆頭著者 責任著者 国際誌
2021年5月

Fibronectin-integrin signaling regulates PLVAP localization at endothelial fenestrae by microtubule stabilization.

Cell and tissue research
  • Takashi Nakakura
  • ,
  • Takeshi Suzuki
  • ,
  • Kotaro Horiguchi
  • ,
  • Hideyuki Tanaka
  • ,
  • Kenjiro Arisawa
  • ,
  • Toshio Miyashita
  • ,
  • Yoko Nekooki-Machida
  • ,
  • Haruo Hagiwara

384
2
開始ページ
449
終了ページ
463
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00441-020-03326-2

Endothelial fenestrae are the transcellular pores existing on the capillary walls which are organized in clusters referred to as sieve plates. They are also divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP). In this study, we examined the involvement of fibronectin signaling in the formation of fenestra and diaphragm in endothelial cells. Results showed that Itga5 and Itgb1 were expressed in PECAM1-positive endothelial cells isolated from the anterior lobe (AL) of the rat pituitary, and integrin α5 was localized at the fenestrated capillaries of the rat pituitary and cultured PECAM1-positive endothelial cells isolated from AL (CECAL). Inhibition of both integrin α5β1 and FAK, a key molecule for integrin-microtubule signaling, respectively, by ATN-161 and FAK inhibitor 14, caused the delocalization of PLVAP at the sieve plates and depolymerization of microtubules in CECAL. Paclitaxel prevented the delocalization of PLVAP by the inhibition of integrin α5β1. Microtubule depolymerization induced by colcemid also caused the delocalization of PLVAP. Treatment of CECAL with ATN-161 and colcemid caused PLVAP localization at the Golgi apparatus. The localization of PLVAP at the sieve plates was inhibited by BFA treatment in a time-dependent manner and spread diffusely to the cytoplasm. These results indicate that a constant supply of PLVAP proteins by the endomembrane system via the Golgi apparatus is essential for the localization of PLVAP at sieve plates. In conclusion, the endomembrane transport pathway from the Golgi apparatus to sieve plates requires microtubule cytoskeletons, which are regulated by fibronectin-integrin α5β1 signaling.

リンク情報
DOI
https://doi.org/10.1007/s00441-020-03326-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33447878
ID情報
  • DOI : 10.1007/s00441-020-03326-2
  • PubMed ID : 33447878

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