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Modulation of host cell mTOR signali...

Wang, Yubao.

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Modulation of host cell mTOR signaling by Toxoplasma gondii.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Modulation of host cell mTOR signaling by Toxoplasma gondii./
作者:	Wang, Yubao.
面頁冊數:	175 p.
附註:	Source: Dissertation Abstracts International, Volume: 70-11, Section: B, page: 6654.
Contained By:	Dissertation Abstracts International70-11B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3385052
ISBN:	9781109489071

Modulation of host cell mTOR signaling by Toxoplasma gondii.
Wang, Yubao.

Modulation of host cell mTOR signaling by Toxoplasma gondii. - 175 p.

Source: Dissertation Abstracts International, Volume: 70-11, Section: B, page: 6654.

Thesis (Ph.D.)--Yeshiva University, 2010.

Toxoplasma gondii, an obligate protozoan parasite, have been demonstrated to employ delicate strategies for infection. The modulation of many aspects of host cell physiology by T. gondii and the related mechanisms largely remains unknown. We hypothesize that parasite infection might modulate host cell growth and metabolism, as well as the related signaling events. We find that T. gondii infection induces host cell autophagy, a bulk degradation pathway. Infection-induced autophagy is independent of mTOR complex 1, mTORC1, and relies on calcium signaling. At physiologically relevant amino acid levels, parasite growth becomes defective in autophagy-deficient cells. Furthermore, infection causes consumption of host cell mass in an autophagy-dependent manner, indicating a role of autophagy in parasite recovery of host cell nutrients. The findings propose a novel function for autophagy as a pathway by which parasites may effectively compete with the host cell for limiting anabolic resources. We also find that T. gondii infection induces rapid and sustained mTORC1 activation, which has non-canonical features. Given the critical role of mTORC1 in controlling cell growth and proliferation, we find that infection drives dramatic host cell cycle entry and progression, which is independent of exogenous mitogenic factors but requires mTORC1 activity. The study represents a pathophysiological demonstration of mTORC1-dependent cell cycle entry and progression. The non-canonical mTORC1 activation, which is induced by parasite infection, provides a unique model for further understanding the mechanisms of mTORC1 signaling. The other mTOR complex, mTORC2, is found to be induced by T. gondii infection in both human and mouse fibroblasts. The mTORC2 signaling is demonstrated to control the polarity of reorganized centrosome in infected cells via Akt effector Gsk3. Disruption of mTORC2/Akt signaling perturbs the astral patterning of microtubules around the parasitophorous vacuole, as well as the pattern of host lysosome and mitochondrial localization around the vacuole. Furthermore we find that infection suppresses scratch-induced cell migration in a mTORC2-dependent manner. These findings imply the novel roles for mTORC2 in the mediation of polarizing responses that control centrosome position, cellular organization and cell migration.

ISBN: 9781109489071Subjects--Topical Terms:

1017686
Biology, Cell.

Modulation of host cell mTOR signaling by Toxoplasma gondii.
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