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Molecular and Cellular Biology, July 2008, p. 4215-4226, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.00867-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Rictor-Myo1c Complex Participates in Dynamic Cortical Actin Events in 3T3-L1 Adipocytes ^,

G. Nana Hagan,¹ Yenshou Lin,^2, Mark A. Magnuson,³ Joseph Avruch,² and Michael P. Czech^1*

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605,¹ Department of Molecular Biology and the Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02114,² Department of Molecular Physiology and Biophysics and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232³

Received 16 May 2007/ Returned for modification 6 July 2007/ Accepted 9 April 2008

Insulin signaling through phosphatidylinositol 3-kinase (PI 3-kinase) activates the protein kinase Akt through phosphorylation of its threonine 308 and serine 473 residues by the PDK1 protein kinase and the Rictor-mammalian target of rapamycin complex (mTORC2), respectively. Remarkably, we show here that the Rictor protein is also present in cultured adipocytes in complexes containing Myo1c, a molecular motor that promotes cortical actin remodeling. Interestingly, the Rictor-Myo1c complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Furthermore, while RNA interference-directed silencing of Rictor results in the expected attenuation of Akt phosphorylation at serine 473, depletion of Myo1c is without effect. In contrast, loss of either Rictor or Myo1c inhibits phosphorylation of the actin filament regulatory protein paxillin at tyrosine 118. Furthermore, Myo1c-induced membrane ruffling of 3T3-L1 adipocytes is also compromised following Rictor knockdown. Interestingly, neither the mTORC2 inhibitor rapamycin nor the PI 3-kinase inhibitor wortmannin affects paxillin tyrosine 118 phosphorylation. Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events.

Published ahead of print on 21 April 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.