TRIM72 modulates caveolar endocytosis in repair of lung cells

Nagaraja Nagre, Shaohua Wang, Thomas Kellett, Ragu Kanagasabai, Jing Deng, Miyuki Nishi, Konstantin Shilo, Richard A. Oeckler, Jack C. Yalowich, Hiroshi Takeshima, John Christman, Rolf D. Hubmayr, Xiaoli Zhao

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Alveolar epithelial and endothelial cell injury is a major feature of the acute respiratory distress syndrome, in particular when in conjunction with ventilation therapies. Previously we showed [Kim SC, Kellett T, Wang S, Nishi M, Nagre N, Zhou B, Flodby P, Shilo K, Ghadiali SN, Takeshima H, Hubmayr RD, Zhao X. Am J Physiol Lung Cell Mol Physiol 307: L449-L459, 2014.] that tripartite motif protein 72 (TRIM72) is essential for amending alveolar epithelial cell injury. Here, we posit that TRIM72 improves cellular integrity through its interaction with caveolin 1 (Cav1). Our data show that, in primary type I alveolar epithelial cells, lack of TRIM72 led to significant reduction of Cav1 at the plasma membrane, accompanied by marked attenuation of caveolar endocytosis. Meanwhile, lentivirus-mediated overexpression of TRIM72 selectively increases caveolar endocytosis in rat lung epithelial cells, suggesting a functional association between these two. Further coimmunoprecipitation assays show that deletion of either functional domain of TRIM72, i.e., RING, B-box, coiled-coil, or PRYSPRY, abolishes the physical interaction between TRIM72 and Cav1, suggesting that all theoretical domains of TRIM72 are required to forge a strong interaction between these two molecules. Moreover, in vivo studies showed that injurious ventilation-induced lung cell death was significantly increased in knockout (KO) TRIM72KO and Cav1KO lungs compared with wild-type controls and was particularly pronounced in double KO mutants. Apoptosis was accompanied by accentuation of gross lung injury manifestations in the TRIM72KO and Cav1KO mice. Our data show that TRIM72 directly and indirectly modulates caveolar endocytosis, an essential process involved in repair of lung epithelial cells through removal of plasma membrane wounds. Given TRIM72’s role in endomembrane trafficking and cell repair, we consider this molecule an attractive therapeutic target for patients with injured lungs.

Original languageEnglish (US)
Pages (from-to)L452-L464
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number5
DOIs
StatePublished - Mar 1 2016

Fingerprint

Endocytosis
Lung
Alveolar Epithelial Cells
Caveolin 1
Ventilation
Wounds and Injuries
Epithelial Cells
Cell Membrane
Lentivirus
Tripartite Motif Proteins
Adult Respiratory Distress Syndrome
Lung Injury
Cell Death
Endothelial Cells
Apoptosis
Therapeutics

Keywords

  • Acute respiratory distress syndrome
  • Alveolar epithelial cells
  • Apoptosis
  • Caveolar endocytosis
  • Lung injury
  • Tripartite motif protein 72

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology (medical)

Cite this

Nagre, N., Wang, S., Kellett, T., Kanagasabai, R., Deng, J., Nishi, M., ... Zhao, X. (2016). TRIM72 modulates caveolar endocytosis in repair of lung cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 310(5), L452-L464. https://doi.org/10.1152/ajplung.00089.2015

TRIM72 modulates caveolar endocytosis in repair of lung cells. / Nagre, Nagaraja; Wang, Shaohua; Kellett, Thomas; Kanagasabai, Ragu; Deng, Jing; Nishi, Miyuki; Shilo, Konstantin; Oeckler, Richard A.; Yalowich, Jack C.; Takeshima, Hiroshi; Christman, John; Hubmayr, Rolf D.; Zhao, Xiaoli.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 5, 01.03.2016, p. L452-L464.

Research output: Contribution to journalArticle

Nagre, N, Wang, S, Kellett, T, Kanagasabai, R, Deng, J, Nishi, M, Shilo, K, Oeckler, RA, Yalowich, JC, Takeshima, H, Christman, J, Hubmayr, RD & Zhao, X 2016, 'TRIM72 modulates caveolar endocytosis in repair of lung cells', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 310, no. 5, pp. L452-L464. https://doi.org/10.1152/ajplung.00089.2015
Nagre, Nagaraja ; Wang, Shaohua ; Kellett, Thomas ; Kanagasabai, Ragu ; Deng, Jing ; Nishi, Miyuki ; Shilo, Konstantin ; Oeckler, Richard A. ; Yalowich, Jack C. ; Takeshima, Hiroshi ; Christman, John ; Hubmayr, Rolf D. ; Zhao, Xiaoli. / TRIM72 modulates caveolar endocytosis in repair of lung cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2016 ; Vol. 310, No. 5. pp. L452-L464.
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