A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes
Hagan, G. Nana ; Lin, Yenshou ; Magnuson, Mark A. ; Avruch, Joseph ; Czech, Michael P.
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UMass Chan Affiliations
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Keywords
3T3-L1 Cells
Actins
Adipocytes
Animals
Carrier Proteins
Cell Membrane Structures
Cells, Cultured
Enzyme Activation
Fibroblasts
Humans
Immunoprecipitation
Insulin
Mice
Myosins
Paxillin
Phosphotyrosine
Protein Binding
Protein Kinases
Protein Structure, Tertiary
Proto-Oncogene Proteins c-akt
Sirolimus
Life Sciences
Medicine and Health Sciences
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Abstract
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.
Source
Mol Cell Biol. 2008 Jul;28(13):4215-26. Epub 2008 Apr 21. Link to article on publisher's site