Core components of endosomal mRNA transport are evolutionarily conserved in fungi

Mueller, Jessica; Pohlmann, Thomas; Feldbruegge, Michael

doi:10.1101/467787

Cited by 5 publications

(9 citation statements)

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“…We observed extensive co-localization in processively moving units, suggesting that the RNA-binding protein GUL1 participates in endosomal mRNA transport (Fig 7C-D; S4 movie). Importantly, this is the first evidence that this mode of long-distance transport is also present in ascomycetes (42). Taken together, our fluorescent microscopic investigation reveals that GUL1 acts close to nuclei and shuttles with PAB1 and transport endosomes along microtubules.…”

Section: B S5 Fig)supporting

confidence: 66%

“…Transport mRNPs are stabilized by the scaffold protein Upa2 and linked to endosomes via the FYVE domain protein Upa1 (41,46). A phylogenetic analysis revealed that important core components of endosomal transport like Upa2 and the key RBP Rrm4 are missing in ascomycetes (42). However, here we demonstrate that numerous RNA-binding proteins containing RRM domains are prominent STRIPAK targets.…”

Section: Gul1 Is Trafficking On Endosomesmentioning

confidence: 63%

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The STRIPAK signaling complex regulates phosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

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et al. 2020

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19 The striatin-interacting phosphatase and kinase (STRIPAK) multi-subunit signaling complex is 20 highly conserved within eukaryotes. In fungi, STRIPAK controls multicellular development, 21 morphogenesis, pathogenicity, and cell-cell recognition, while in humans, certain diseases are 22 related to this signaling complex. To date, phosphorylation and dephosphorylation targets of 23 STRIPAK are still widely unknown in microbial as well as animal systems. Here, we provide 24 an extended global proteome and phosphoproteome study using the wild type as well as 25 STRIPAK single and double deletion mutants from the filamentous fungus 26 Sordaria macrospora. Notably, in the deletion mutants, we identified the differential 27 phosphorylation of 129 proteins, of which 70 phosphorylation sites were previously unknown.28 Included in the list of STRIPAK targets are eight proteins with RNA recognition motifs (RRMs) 29 including GUL1. Knockout mutants and complemented transformants clearly show that GUL1 30 affects hyphal growth and sexual development. To assess the role of GUL1 phosphorylation on 31 fungal development, we constructed phospho-mimetic and -deficient mutants of GUL1 residues 32 S180, S216, and S1343. While the S1343 mutants were indistinguishable from wildtype, 33 phospho-deficiency of S180 and S216 resulted in a drastic reduction in hyphal growth and 34 phospho-deficiency of S216 also affects sexual fertility. These results thus suggest that 35 differential phosphorylation of GUL1 regulates developmental processes such as fruiting body 36 maturation and hyphal morphogenesis. Moreover, genetic interaction studies provide strong 37 evidence that GUL1 is not an integral subunit of STRIPAK. Finally, fluorescence microcopy 38 revealed that GUL1 co-localizes with endosomal marker proteins and shuttles on endosomes.39 Here, we provide a new mechanistic model that explains how STRIPAK-dependent and -40 independent phosphorylation of GUL1 regulates sexual development and asexual growth. 41 3 42 Author Summary43 In eukaryotes, the striatin-interacting phosphatase and kinase (STRIPAK) multi-subunit 44 signaling complex controls a variety of developmental processes, and the lack of single 45 STRIPAK subunits is associated with severe developmental defects and diseases. However, in 46 humans, animals, as well as fungal microbes, the phosphorylation and dephosphorylation 47 targets of STRIPAK are still largely unknown. The filamentous fungus Sordaria macrospora 48 is a well-established model system used to study the function of STRIPAK, since a collection 49 of STRIPAK mutants is experimentally accessible. We previously established an isobaric tag 50 for relative and absolute quantification (iTRAQ)-based proteomic and phosphoproteomic 51 analysis to identify targets of STRIPAK. Here, we investigate mutants that lack one or two 52 STRIPAK subunits. Our analysis resulted in the identification of 129 putative phosphorylation 53 targets of STRIPAK including GUL1, a homolog of the RNA-binding protein SSD1 from yeast. 54 Using f...

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Section: B S5 Fig)supporting

confidence: 66%

Section: Gul1 Is Trafficking On Endosomesmentioning

confidence: 63%

The STRIPAK signaling complex regulates phosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

Stein

Blank-Landeshammer

Müntjes

et al. 2020

Preprint

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“…We observed extensive co-localization in processively moving units of about 91%, suggesting that the RNA-binding protein GUL1 participates in endosomal mRNA transport ( Fig 8 ; S9 Movie , S5 Dataset ). Importantly, this is the first evidence that this mode of long-distance transport is also present in a euascomycete [ 52 ]. Taken together, our fluorescent microscopic investigation reveals that GUL1 acts close to nuclei and shuttles with Pab1 most likely on Rab5-positive-endosomes along microtubules.…”

Section: Resultsmentioning

confidence: 95%

“…Transport mRNPs are stabilized by the scaffold protein Upa2 and linked to endosomes via the FYVE domain protein Upa1 [ 51 , 56 ]. A phylogenetic analysis revealed that important core components of endosomal transport like Upa2 and the key RBP Rrm4 are missing in ascomycetes [ 52 ]. However, here we demonstrate that numerous RNA-binding proteins containing RRM domains are prominent STRIPAK targets.…”

Section: Discussionmentioning

confidence: 99%

The STRIPAK signaling complex regulates dephosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

et al. 2020

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The striatin-interacting phosphatase and kinase (STRIPAK) multi-subunit signaling complex is highly conserved within eukaryotes. In fungi, STRIPAK controls multicellular development, morphogenesis, pathogenicity, and cell-cell recognition, while in humans, certain diseases are related to this signaling complex. To date, phosphorylation and dephosphorylation targets of STRIPAK are still widely unknown in microbial as well as animal systems. Here, we provide an extended global proteome and phosphoproteome study using the wild type as well as STRIPAK single and double deletion mutants (Δpro11, Δpro11Δpro22,

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“…Consistent with the notion that Rrm4, Upa1 and Upa2 function together, these fungi also had orthologs for Rrm4 and Upa1. Notably, Upa2 was absent in Malassezia globosa , which presumably has lost the endosomal mRNA transport machinery, because it lacks a clear ortholog of Rrm4 (Fig C) . In essence, the evolutionarily conserved Upa2 is a novel factor essential for efficient unipolar growth that might function in endosomal mRNA transport.…”

Section: Resultsmentioning

confidence: 99%

The multi PAM 2 protein Upa2 functions as novel core component of endosomal mRNA transport

et al. 2019

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mRNA transport determines spatiotemporal protein expression. Transport units are higher‐order ribonucleoprotein complexes containing cargo mRNAs, RNA‐binding proteins and accessory proteins. Endosomal mRNA transport in fungal hyphae belongs to the best‐studied translocation mechanisms. Although several factors are known, additional core components are missing. Here, we describe the 232 kDa protein Upa2 containing multiple PAM2 motifs (poly[A]‐binding protein [Pab1]‐associated motif 2) as a novel core component. Loss of Upa2 disturbs transport of cargo mRNAs and associated Pab1. Upa2 is present on almost all transport endosomes in an mRNA‐dependent manner. Surprisingly, all four PAM2 motifs are dispensable for function during unipolar hyphal growth. Instead, Upa2 harbours a novel N‐terminal effector domain as important functional determinant as well as a C‐terminal GWW motif for specific endosomal localisation. In essence, Upa2 meets all the criteria of a novel core component of endosomal mRNA transport and appears to carry out crucial scaffolding functions.

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Core components of endosomal mRNA transport are evolutionarily conserved in fungi

Cited by 5 publications

References 17 publications

The STRIPAK signaling complex regulates phosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

The STRIPAK signaling complex regulates phosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

The STRIPAK signaling complex regulates dephosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

The multi PAM 2 protein Upa2 functions as novel core component of endosomal mRNA transport

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