Characterization of the interactomes of YAP and TAZ in podocytes identifies a relation between YAP and TAZ and proteins of the nuclear shuttling machinery

ABSTRACT: The two effector proteins of the Hippo signaling pathway, YAP and TAZ, play a pivotal role in the cellular homeostasis of podocytes and in the pathogenesis of focal segmental glomerulosclerosis (FSGS). We aim to unravel the unique and redundant functions of YAP and TAZ in the podocyte by identifying podocyte-specific interactors. We generated stable heat sensitive mouse podocytes (hsMPs) carrying a single copy integration of a transgenic construct expressing a flagged version of mouse Yap (3XFLAG.YAP), Taz (3XFLAG.TAZ) or Ruby (3XFLAG.RUBY) in the Rosa26 locus. To explore the interactome of YAP and TAZ in podocytes we immunoprecipitated the tagged proteins and characterized the co-immunoprecipitated protein complexes by mass spectrometry. Within the interactome analyses of the hsMPs, we identified shared and non-shared interacting proteins between YAP and TAZ. Among these identified proteins many well established interactors of YAP and TAZ were included, like proteins of the Tead family, different angiomotins or large tumor suppressor kinase 1 (Lats1). Strikingly, among the shared proteins were numerous proteins of the nuclear shuttling machinery, like importins (Ipo), exportins (Xpo), transportins (Tnpo) and nucleoporins (Nup) that form the nuclear pore complex (NPC), such as NUP107, NUP133, NUP205 and XPO5.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Prerana Wagle  

LAB HEAD: Bernhard Schermer

PROVIDER: PXD040448 | Pride | 2024-01-26

REPOSITORIES: Pride