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Supervillin Binds The Rac/Rho-Gef Trio And Increases Trio-Mediated Rac1 Activation, Kyonghee Son, Tara Smith, Elizabeth Luna
Supervillin Binds The Rac/Rho-Gef Trio And Increases Trio-Mediated Rac1 Activation, Kyonghee Son, Tara Smith, Elizabeth Luna
Elizabeth J. Luna
We investigated cross-talk between the membrane-associated, myosin II-regulatory protein supervillin and the actin-regulatory small GTPases Rac1, RhoA, and Cdc42. Supervillin knockdown reduced Rac1-GTP loading, but not the GTP loading of RhoA or Cdc42, in HeLa cells with normal levels of the Rac1-activating protein Trio. No reduction in Rac1-GTP loading was observed when supervillin levels were reduced in Trio-depleted cells. Conversely, overexpression of supervillin isoform 1 (SV1) or, especially, isoform 4 (SV4) increased Rac1 activation. Inhibition of the Trio-mediated Rac1 guanine nucleotide exchange (GEF) activity with ITX3 partially blocked the SV4-mediated increase in Rac1-GTP. Both SV4 and SV1 co-localized with Trio …
Gamma-Sarcoglycan Is Required For The Response Of Archvillin To Mechanical Stimulation In Skeletal Muscle, Janelle Spinazzola, Tara Smith, Min Liu, Elizabeth Luna, Elisabeth Barton
Gamma-Sarcoglycan Is Required For The Response Of Archvillin To Mechanical Stimulation In Skeletal Muscle, Janelle Spinazzola, Tara Smith, Min Liu, Elizabeth Luna, Elisabeth Barton
Elizabeth J. Luna
Loss of gamma-sarcoglycan (gamma-SG) induces muscle degeneration and signaling defects in response to mechanical load, and its absence is common to both Duchenne and limb girdle muscular dystrophies. Growing evidence suggests that aberrant signaling contributes to the disease pathology; however, the mechanisms of gamma-SG-mediated mechanical signaling are poorly understood. To uncover gamma-SG signaling pathway components, we performed yeast two-hybrid screens and identified the muscle-specific protein archvillin as a gamma-SG and dystrophin interacting protein. Archvillin protein and message levels were significantly upregulated at the sarcolemma of murine gamma-SG-null (gsg-/-) muscle but delocalized in dystrophin-deficient mdx muscle. Similar elevation of archvillin protein …