Regulation of Blood–Testis Barrier (BTB) Dynamics during Spermatogenesis via the “Yin” and “Yang” Effects of Mammalian Target of Rapamycin Complex 1 (mTORC1) and mTORC2 - International Review of Cell and Molecular Biology - page 315

3. MAMMALIAN TARGET OF RAPAMYCIN (mTOR)
3.1. Introduction
The discovery of TOR, a Ser/Thr protein kinase, in yeasts was aided by
using an antibiotic called rapamycin, which was found to specifically inhibit
the activity of TOR and was thus designated “target of rapamycin (TOR).”
Subsequent studies have identified its homolog in mammalian cells desig-
nated mammalian target of rapamycin (mTOR) ( Brown et al., 1994 ; Chiu
et al., 1994 ; Sabatini et al., 1994 ). Much attention was drawn to mTOR
for its essential role in cell growth and proliferation as mTOR is the key
regulator for sensing and integrating diverse environmental clues includ-
ing growth factors, mitogens and nutrients so that appropriate cellular
responses can occur in response to these changes ( Laplante and Sabatini,
2012 ). Subsequent studies have shown that mTOR, besides protein synthe-
sis that affects cell growth and proliferation, is virtually involved in almost
all aspects of cellular function such as actin cytoskeleton reorganization, cell
survival, and autophagy ( Appenzeller-Herzog and Hall, 2012 ; Chi, 2012 ;
Laplante and Sabatini, 2012 ; Nair and Ren, 2012 ), as well as pathogenesis
such as carcinogenesis ( Ekman et al., 2012 ; Fasolo and Sessa, 2012 ; Lieber-
thal and Levine, 2012 ; Posadas and Figlin, 2012 ; Sheppard et al., 2012 ).
Dysregulation of mTOR signaling is observed in different pathological
conditions, such as diabetes, cancer and obesity ( Weichhart, 2012 ; Zoncu
et al., 2011 ). mTOR belongs to PIKK (PI3K-related kinase) superfam-
ily as its C-terminus shares strong homology to the catalytic domain of
PI3K. However, instead of being a lipid kinase, mTOR is a Ser/Thr pro-
tein kinase. In order to execute its cellular functions, mTOR forms one of
the two complexes, namely mTORC1 and mTORC2, by associating with
different binding partners ( Dazert and Hall, 2011 ; Laplante and Sabatini,
2012 ). mTORC1 is composed of mTOR, regulatory associated protein of
mTOR (raptor), PRAS40, mLST8 and deptor. mTORC1 is responsible for
the well-known roles of mTOR that regulates cell growth and prolifera-
tion by modulating protein synthesis. Moreover, mTORC1 is sensitive to
rapamycin, which acts as an allosteric inhibitor for mTORC1 by associat-
ing with FKBP12 to form a complex. This complex binds to mTOR in
a short stretch of sequence near its C-terminus known as the FKBP12-
rapamycin-binding domain, causing dissociation of raptor from mTORC1
( Senqupta et al., 2010 ; Zhou and Huang, 2010 ). And for another mTOR
complex, the mTORC2 was first described as rapamycin insensitive as