Martin Helmstädter

Publications (2)10.15 Total impact

• Source

  Available from: Ashish Ashish

  Article: Functional study of mammalian Neph proteins in Drosophila melanogaster.

  Martin Helmstädter, Kevin Lüthy, Markus Gödel, Matias Simons, Ashish, Deepak Nihalani, Stefan A Rensing, Karl-Friedrich Fischbach, Tobias B Huber
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  ABSTRACT: Neph molecules are highly conserved immunoglobulin superfamily proteins (IgSF) which are essential for multiple morphogenetic processes, including glomerular development in mammals and neuronal as well as nephrocyte development in D. melanogaster. While D. melanogaster expresses two Neph-like proteins (Kirre and IrreC/Rst), three Neph proteins (Neph1-3) are expressed in the mammalian system. However, although these molecules are highly abundant, their molecular functions are still poorly understood. Here we report on a fly system in which we overexpress and replace endogenous Neph homologs with mammalian Neph1-3 proteins to identify functional Neph protein networks required for neuronal and nephrocyte development. Misexpression of Neph1, but neither Neph2 nor Neph3, phenocopies the overexpression of endogenous Neph molecules suggesting a functional diversity of mammalian Neph family proteins. Moreover, structure-function analysis identified a conserved and specific Neph1 protein motif that appears to be required for the functional replacement of Kirre. Hereby, we establish D. melanogaster as a genetic system to specifically model molecular Neph1 functions in vivo and identify a conserved amino acid motif linking Neph1 to Drosophila Kirre function.
  PLoS ONE 01/2012; 7(7):e40300. · 4.09 Impact Factor
• Source

  Available from: Karl-Friedrich Fischbach

  Article: The BAR domain protein PICK1 regulates cell recognition and morphogenesis by interacting with Neph proteins.

  Martin Höhne, Johannes Lorscheider, Anna von Bardeleben, Matthias Dufner, M Antonia Scharf, Markus Gödel, Martin Helmstädter, Eva-Maria Schurek, Sibylle Zank, Peter Gerke, Christine Kurschat, Sema Hayriye Sivritas, Elke Neumann-Haefelin, Tobias B Huber, H Christian Reinhardt, Astrid C Schauss, Bernhard Schermer, Karl-Friedrich Fischbach, Thomas Benzing
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  ABSTRACT: Neph proteins are evolutionarily conserved membrane proteins of the immunoglobulin superfamily that control the formation of specific intercellular contacts. Cell recognition through these proteins is essential in diverse cellular contexts such as patterning of the compound eye in Drosophila melanogaster, neuronal connectivity in Caenorhabditis elegans, and the formation of the kidney filtration barrier in mammals. Here we identify the PDZ and BAR domain protein PICK1 (protein interacting with C-kinase 1) as a Neph-interacting protein. Binding required dimerization of PICK1, was dependent on PDZ domain protein interactions, and mediated stabilization of Neph1 at the plasma membrane. Moreover, protein kinase C (PKCα) activity facilitated the interaction through releasing Neph proteins from their binding to the multidomain scaffolding protein zonula occludens 1 (ZO-1), another PDZ domain protein. In Drosophila, the Neph homologue Roughest is essential for sorting of interommatidial precursor cells and patterning of the compound eye. RNA interference-mediated knockdown of PICK1 in the Drosophila eye imaginal disc caused a Roughest destabilization at the plasma membrane and a phenotype that resembled rst mutation. These data indicate that Neph proteins and PICK1 synergistically regulate cell recognition and contact formation.
  Molecular and cellular biology 06/2011; 31(16):3241-51. · 6.06 Impact Factor