Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells.
The mammalian target of rapamycin (mTOR) assembles into two different multi-protein complexes, mTORC1 and mTORC2. The mTORC2 complex is distinct due to the unique expression of the specific core regulatory protein Rictor (rapamycin-insensitive companion of mTOR). mTORC2 has been implicated in regulating actin cytoskeletal reorganization but its role in gonadotrope function is unknown. Using the gonadotrope-derived LβT2 cell line, we find that the GnRH agonist buserelin (GnRHa) phosphorylates both mTOR and Rictor. Interestingly, inhibition of mTORC2 blunts GnRHa-induced cyto-architectural rearrangements. Coincident with blunting of actin reorganization, inhibition of mTORC2 also attenuates GnRHa-mediated activation of both protein kinase C (PKC) and extracellular signal regulated kinase (ERK). Collectively, our data suggests that GnRHa-mediated mTORC2 activation is important in facilitating actin reorganization events critical for initiating PKC activity and subsequent ERK phosphorylation in the gonadotrope-derived LβT2 cell line.
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: b80@uwyo.edu.
Brian S
BS
Edwards
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: wyoisom@gmail.com.
William J
WJ
Isom
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: anavrati@uwyo.edu.
Amy M
AM
Navratil
D000199:Actins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D052681:Gonadotrophs / Q000187:drug effects / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; D007987:Gonadotropin-Releasing Hormone; D000076225:Mechanistic Target of Rapamycin Complex 2; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases
Actin; ERK; Gonadotrope; Mammalian target of rapamycin complex 2; PKC
Endocrinology. 2016 Feb;157(2):831-43
26696122
J Biol Chem. 2004 Dec 10;279(50):52500-16
15448167
Mol Endocrinol. 2011 May;25(5):810-20
21372146
Mol Cell Endocrinol. 2009 Nov 13;311(1-2):47-54
19632296
Biochim Biophys Acta. 2014 Feb;1838(2):532-45
23899502
Mol Endocrinol. 2009 Jul;23(7):1092-101
19372235
Oncogene. 2010 Jul 1;29(26):3733-44
20418915
J Biol Chem. 2004 Jan 16;279(3):1980-93
14559894
Science. 2005 Feb 18;307(5712):1098-101
15718470
Curr Biol. 2002 Jul 23;12(14):1251-5
12176337
Mol Cell. 2011 Apr 8;42(1):50-61
21474067
Mol Cell Endocrinol. 2014 Mar 25;385(1-2):78-87
24035865
Mol Cell Biol. 1999 Apr;19(4):2567-76
10082522
Nat Cell Biol. 2004 Nov;6(11):1122-8
15467718
Mol Endocrinol. 2000 Nov;14(11):1811-9
11075814
Mol Endocrinol. 1997 Jun;11(6):738-46
9171237
Brain Res. 2010 Dec 10;1364:53-61
20836995
Mol Endocrinol. 2002 Mar;16(3):419-34
11875099
Cell. 2006 Oct 6;127(1):125-37
16962653
Mol Endocrinol. 1991 Mar;5(3):347-55
1653891
Mol Endocrinol. 1999 May;13(5):752-63
10319325
Mol Endocrinol. 2007 Feb;21(2):538-49
17068198
Cell. 2007 Jun 29;129(7):1261-74
17604717
Mol Endocrinol. 2014 Dec;28(12):2049-59
25333516
J Biol Chem. 2007 Dec 14;282(50):36682-91
17947241
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14509-14
21873248
Curr Biol. 2006 Sep 19;16(18):1865-70
16919458
Mol Cell Neurosci. 1992 Apr;3(2):124-32
19912852
Mol Cell Endocrinol. 2014 Jan 25;382(1):346-57
24161835
Nat Cell Biol. 2002 Sep;4(9):648-57
12172553
Science. 1996 Aug 30;273(5279):1219-21
8703054
Cell. 2009 May 29;137(5):873-86
19446321
Mol Cell. 2002 Jul;10 (1):151-62
12150915
Curr Biol. 2004 Jul 27;14(14):1296-302
15268862
Mol Cell. 2008 Oct 10;32(1):140-9
18851840
J Biol Chem. 2003 Aug 22;278(34):31593-602
12791688
Endocrinology. 2007 Apr;148(4):1736-44
17218416
Mol Endocrinol. 2004 May;18(5):1301-12
14752057
Endocrinology. 2014 Feb;155(2):548-57
24274984