Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling

Molecular Biology of the Cell
Mark C WilkesEdward B Leof

Abstract

Transforming growth factor β (TGFβ) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFβ's actions reflect the activity of a number of signaling networks, the primary mediator of TGFβ responses are the Smad proteins. Following receptor activation, these cytoplasmic proteins form hetero-oligomeric complexes that translocate to the nucleus and affect gene transcription. Here, through biological, biochemical, and immunofluorescence approaches, sorting nexin 9 (SNX9) is identified as being required for Smad3-dependent responses. SNX9 interacts with phosphorylated (p) Smad3 independent of Smad2 or Smad4 and promotes more rapid nuclear delivery than that observed independent of ligand. Although SNX9 does not bind nucleoporins Nup153 or Nup214 or some β importins (Imp7 or Impβ), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9.

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Citations

Dec 1, 2017·Acta Biochimica Et Biophysica Sinica·Feng XieLong Zhang
Mar 17, 2019·Clinical Science·Jian YangChunyu Zeng
Mar 1, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Makoto OkanoMotoyuki Itoh
May 23, 2017·The Journal of Clinical Investigation·Jeong-Han KangEdward B Leof
Oct 14, 2020·The International Journal of Biochemistry & Cell Biology·Jun ShiYuyi Mai
Oct 23, 2020·Journal of Cellular Physiology·Lu YangJing Zhong

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Methods Mentioned

BETA
nuclear translocation
pull down
immunoprecipitation
co-IP
pull-down
confocal microscopy
transfection
GTPase

Software Mentioned

MetaMorph

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