Understanding signaling through the “striatin interacting phosphatase and kinase” (STRIPAK) complex in eukaryotic development

Striatin-interacting phosphatase and kinase (STRIPAK) complexes are supramolecular structures that are evolutionary conserved from yeast to man. Molecular genetic analysis has shown that diverse processes are STRIPAK complex dependent, such as mammalian cell proliferation, differentiation, and embryonic development, autophagosome transport in Drosophila neurons, viability of Caenorhabditis elegans embryos or cellular fusion and organ formation in microbial systems. Further, medical studies revealed that dysregulation of STRIPAK complexes are correlated with diverse human diseases, including cancer.
Recently, several reports have provided evidence that STRIPAK complexes are regulators or mediators of vital highly conserved cell signaling pathways in eukaryotes. However, the precise targets of phosphorylation and dephosphorylation by STRIPAK associated kinases are not yet defined.

Quantitative phosphoproteomic analysis

Experimental projects:

•     Phosphoproteome from S. macrospora: Identification of target proteins that are phosphorylated/dephosphorylated by subunits of the STRIPAK complex
•     Functional in-vivo analysis of phospho-deficient and phospho-mimetic variants of putative STRIPAK targets

References

Blank-Landeshammer B, Teichert I, Märker R, Nowrousian M, Kück U, Sickmann A (2019) Combination of proteogenomics with peptide de novo sequencing identifies new genes and hidden posttranscriptional modifications. mBio 10(5) pii: e02367-19. doi: 10.1128/mBio.02367-19

Märker R, Blank-Landeshammer B, Beier-Rosberger A, Sickmann A, Kück U (2020) Phosphoproteomic analysis of STRIPAK mutants identifies a conserved serine phosphorylation site in PAK kinase CLA4 to be important in fungal sexual development and polarized growth. Molec Microbiol 113:1053–1069.  doi: 10.1111/mmi

Schmidt S, Märker R, Ramšak B, Beier-Rosberger AM, Teichert I, Kück U (2020) Crosstalk between pheromone signaling and NADPH oxidase complexes coordinates fungal developmental processes. Frontiers in Microbiol 11:1722. doi: 10.3389/fmicb.2020.01722

Stein V, Blank-Landeshammer B, Müntjes K, Märker R, Teichert I, Feldbrügge M, Sickmann A, Kück U (2020) The STRIPAK signaling complex regulates dephosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes. PLoS Genetics 16(9):e1008819. doi: 10.1371/journal.pgen.1008819

Stein V, Blank-Landeshammer B, Märker R, Sickmann A, Kück U (2021) Targeted quantification of phosphorylation sites identifies STRIPAK-dependent phosphorylation of the Hippo pathway-related kinase SmKIN3. mBio 12(3):e00658-21. doi: 10.1128/mBio.00658-21

Kück U, Stein V (2021) STRIPAK, a key regulator of fungal development, operates as a multifunctional signaling hub. J. Fungi 7, 443. https://doi.org/10.3390/jof7060443