<scp>HAM</scp>‐2 and <scp>HAM</scp>‐3 are central for the assembly of the <i><scp>N</scp>eurospora</i> <scp>STRIPAK</scp> complex at the nuclear envelope and regulate nuclear accumulation of the <scp>MAP</scp> kinase <scp>MAK</scp>‐1 in a <scp>MAK</scp>‐2‐dependent manner

Dettmann, Anne; Heilig, Yvonne; Ludwig, Sarah; Schmitt, Kerstin; Illgen, Julia; Fleißner, André; Valerius, Oliver; Seiler, Stephan

doi:10.1111/mmi.12399

Cited by 74 publications

(142 citation statements)

References 73 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…5A). This is consistent with previously published data from N. crassa (26). However, some of the PRO45 patches did not colocalize with the ER marker DsRed-KDEL.…”

Section: Resultssupporting

confidence: 93%

“…7B). Our data suggest that STRIPAK subunits PRO11 and PRO22 are required for nuclear envelope localization of PRO45 in S. macrospora, as described for N. crassa (26). Remarkably, the association of PRO45 with mitochondria was retained in the STRIPAK mutants.…”

Section: Slmap In Fungal Developmentsupporting

confidence: 72%

“…Recently, S. cerevisiae PRO45 homologs Far9p and Far10p were reported to remain at the nuclear envelope, even in the absence of all other Far complex components (51). However, in N. crassa, targeting of PRO45 homolog HAM-4 to the nuclear envelope depends on PRO11 homolog HAM-3 and PRO22 homolog HAM-2 (26). To assess PRO45 localization in mutants lacking the S. macrospora STRIPAK component PRO11 or PRO22, we transformed plasmids carrying EGFP-PRO45 into sterile ⌬pro11 and ⌬pro22 mutants (30).…”

Section: Resultsmentioning

confidence: 99%

“…The S. pombe SIP (SIN [septation initiation network] inhibitory PP2A) complex is required for the coordination of mitosis and cytokinesis by inhibiting SIN (16). The N. crassa STRIPAK complex controls nuclear accumulation of the MAK1 mitogen-activated protein (MAP) kinase and regulates chemotropic interactions between conidial germlings (26). Moreover, in the fungal model organism Sordaria macrospora (27)(28)(29), the STRIPAK complex is required for cell fusion and sexual reproduction, namely, the formation of multicellular fruiting bodies (30).…”

mentioning

confidence: 99%

See 3 more Smart Citations

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

et al. 2015

View full text Add to dashboard Cite

bSarcolemmal membrane-associated protein (SLMAP) is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. Further, SLMAP misexpression is associated with endothelial dysfunctions in diabetes and cancer. SLMAP is part of the conserved striatin-interacting phosphatase and kinase (STRIPAK) complex required for specific signaling pathways in yeasts, filamentous fungi, insects, and mammals. In filamentous fungi, STRIPAK was initially discovered in Sordaria macrospora, a model system for fungal differentiation. Here, we functionally characterize the STRIPAK subunit PRO45, a homolog of human SLMAP. We show that PRO45 is required for sexual propagation and cell-to-cell fusion and that its forkhead-associated (FHA) domain is essential for these processes. Protein-protein interaction studies revealed that PRO45 binds to STRIPAK subunits PRO11 and SmMOB3, which are also required for sexual propagation. Superresolution structured-illumination microscopy (SIM) further established that PRO45 localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. SIM also showed that localization to the nuclear envelope requires STRIPAK subunits PRO11 and PRO22, whereas for mitochondria it does not. Taken together, our study provides important insights into fundamental roles of the fungal SLMAP homolog PRO45 and suggests STRIPAK-related and STRIPAK-unrelated functions. Membrane recruitment of protein complexes, cell signaling modules, and enzymes is a critical step for many cellular functions. The family of tail-anchored proteins is recognized for anchoring proteins and vesicles to specific membranes, such as the endoplasmic reticulum (ER) and the outer mitochondrial membrane (1), and tail-anchored proteins are characterized by a C-terminal single transmembrane domain, which is posttranslationally inserted into membranes (2, 3).Sarcolemmal membrane-associated protein (SLMAP) is a tailanchored protein first identified in myocardiac cells (4). In mammals, this protein is known to be involved in myoblast fusion during embryonic development, excitation-contraction coupling in cardiac myocytes, and cell cycle progression (5-8). Furthermore, SLMAP was identified to be a disease gene for Brugada syndrome, a cardiac channelopathy (9). The functional diversity of SLMAP is dependent on alternative splicing, leading to at least four different isoforms of the protein (4, 6, 7, 10). Importantly, gene expression analyses have implicated SLMAP misexpression with endothelial dysfunctions in diabetes, chromosomal aberrations, and cancer (11-14), and currently, SLMAP is the target of lectin-based treatment of drug-resistant cancer cells (15).SLMAP is conserved from yeasts to humans, and characterized fungal SLMAP homologs include Neurospora crassa HAM-4 (hyphal anastomosis 4), Saccharomyces cerevisiae Far9p (factor arrest 9p) and Far10p, as well as Schizosaccharomyces pombe Csc1p (component of SIP complex 1p) (16-18). HAM-4 is essential for vegetativ...

show abstract

“…5A). This is consistent with previously published data from N. crassa (26). However, some of the PRO45 patches did not colocalize with the ER marker DsRed-KDEL.…”

Section: Resultssupporting

confidence: 93%

Section: Slmap In Fungal Developmentsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Genes important for germling/hyphal fusion include genes of the MAK-2 MAP kinase pathway and upstream factors (Fu et al 2011;Dettmann et al 2014), members of the cell wall integrity (CWI) MAP kinase pathway (Fu et al 2011(Fu et al , 2014, the STRIPAK complex (Simonin et al 2010;Dettmann et al 2013), the NADPH oxidation complex (Cano-Dominguez et al 2008;Fu et al 2011Fu et al , 2014, a number of transcription factors (Aldabbous et al 2010;Fu et al 2011;Leeder et al 2013), and genes encoding uncharacterized proteins (Fu et al 2011(Fu et al , 2014. Previously, we showed that HAM-5-GFP localizes to puncta in Dmak-2, Dham-7, and Dham-11 fusion mutants (Jonkers et al 2014).…”

Section: Ham-5 Localization Is Not Disrupted In Other Fusion Mutantsmentioning

confidence: 99%

Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14

et al. 2016

View full text Add to dashboard Cite

In filamentous fungi, communication is essential for the formation of an interconnected, multinucleate, syncytial network, which is constructed via hyphal fusion or fusion of germinated asexual spores (germlings). Anastomosis in filamentous fungi is comparable to other somatic cell fusion events resulting in syncytia, including myoblast fusion during muscle differentiation, macrophage fusion, and fusion of trophoblasts during placental development. In Neurospora crassa, fusion of genetically identical germlings is a highly dynamic and regulated process that requires components of a MAP kinase signal transduction pathway. The kinase pathway components (NRC-1, MEK-2 and MAK-2) and the scaffold protein HAM-5 are recruited to hyphae and germling tips undergoing chemotropic interactions. The MAK-2/HAM-5 protein complex shows dynamic oscillation to hyphae/germling tips during chemotropic interactions, and which is out-of-phase to the dynamic localization of SOFT, which is a scaffold protein for components of the cell wall integrity MAP kinase pathway. In this study, we functionally characterize HAM-5 by generating ham-5 truncation constructs and show that the N-terminal half of HAM-5 was essential for function. This region is required for MAK-2 and MEK-2 interaction and for correct cellular localization of HAM-5 to "fusion puncta." The localization of HAM-5 to puncta was not perturbed in 21 different fusion mutants, nor did these puncta colocalize with components of the secretory pathway. We also identified HAM-14 as a novel member of the HAM-5/MAK-2 pathway by mining MAK-2 phosphoproteomics data. HAM-14 was essential for germling fusion, but not for hyphal fusion. Colocalization and coimmunoprecipitation data indicate that HAM-14 interacts with MAK-2 and MEK-2 and may be involved in recruiting MAK-2 (and MEK-2) to complexes containing HAM-5.KEYWORDS cell fusion; Neurospora crassa; MAP kinase signaling; protein complexes; chemotropism F USION between genetically identical cells exists in many organisms and plays an important role in different developmental processes, for example, myoblast fusion during the formation of muscle tissue, macrophage fusion, or fusion of trophoblasts in placental development (Chen and Olson 2005;Aguilar et al. 2013). In fungi, vegetative fusion enables a fungal colony to share resources and has implications for fitness and virulence (Craven et al. 2008;Fricker et al. 2009;Eaton et al. 2011;Richard et al. 2012;Simonin et al. 2012;Roper et al. 2013;Chagnon 2014). In the filamentous ascomycete fungus, Neurospora crassa, genetically identical germinated asexual spores (germlings) undergo fusion to form a syncytium that is an interconnected network of fused cells Leeder et al. 2013;Herzog et al. 2015). An important pathway required for both germling and hyphal fusion is a conserved mitogen-activated protein kinase (MAPK) cascade that includes the MAPK kinase kinase NRC-1, the MAPK kinase MEK-2, the MAPK MAK-2, and the scaffold protein, HAM-5 (Pandey et al. 2004;Dettmann et al. 2012Dettm...

show abstract

Septum Formation and Cytokinesis in Ascomycete Fungi

Seiler

Heilig

2019

Biology of the Fungal Cell

View full text Add to dashboard Cite

HAM‐2 and HAM‐3 are central for the assembly of the Neurospora STRIPAK complex at the nuclear envelope and regulate nuclear accumulation of the MAP kinase MAK‐1 in a MAK‐2‐dependent manner

Cited by 74 publications

References 73 publications

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14

Septum Formation and Cytokinesis in Ascomycete Fungi

Contact Info

Product

Resources

About