FISCHBACH Laboratory - Martin Helmstaedter

FISCHBACH Laboratory

Martin Helmstaedter

PhD Student

In vivo analysis of mammalian Neph-protein function in Drosophila melanogaster

Project Description

The human Neph-protein family is represented by Neph1, Neph2 and Neph3. Since these proteins are members of the IRM-protein family which is conserved from C. elegans to mammals, genetic studies using the model organism Drosophila melanogaster are helpful to understand the cellular functions of these proteins. We created fly strains that express the mammalian Neph-proteins under the control of an upstream activating sequence (UAS) from yeast. This enables us to specifically target their expression to a defined cell population by crossing these flies to those who express the UAS binding transcription factor Gal4 in a defined spatial and temporal pattern. The Neph orthologs Irregular chiasm C/Roughest (IrreC/Rst) and Kin of irre (Kirre) are known to play an important role in diverse developmental processes like muscle fusion, eye-development and axonal pathfinding in Drosophila. Using the Gal4/UAS system we missexpressed the mammalian Neph-proteins in cells that are known to rely on the correct amount of IrreC/Rst and Kirre. The eye of Drosophila is a crystal like structure arranged by cell sorting that is mediated by the interaction of IrreC/Rst and Kirre with their heterophilic binding partners Sticks and stones (SNS) and Hibris (Hbs). An overexpression of these proteins in cone cells of a developing eye imaginal disc leads to a rough eye phenotype that can be mimicked by Neph1. A misexpression of Neph1 in neurons and glial cells of the optic lobe also leads to a phenocopy of the IrreC/Rst overexpression phenotype. Interestingly, in all our test systems Neph1 is able to copy the phenotypes that are observed by overexpression of IrreC/Rst or Kirre, whereas Neph2 and Neph3 are not. From this data we conclude that of the human slit diaphragm associated Neph proteins, Neph1 is functionally most closely related to the Drosophila Neph-like proteins IrreC/Rst and Kirre and we here identify Drosophila as a genetic system to specifically model molecular Neph1 functions in vivo.


2001 - 2008Study of Biology at the Albert-Ludwigs-University, Freiburg, Germany
2007 - 2008Diploma Thesis 'Charkterisierung transgener Mooslinien mit modifiziertem Glykosylierungsmuster zur Produktion pharmazeutischer Proteine'
since 2008 Albert-Ludwigs-University, Freiburg, Germany, Ph.D. student with Prof. Dr. Karl-Friedrich Fischbach and Prof. Dr. Tobias B. Huber.


Functional Study of Mammalian Neph Proteins in Drosophila melanogaster
PloS one (2012) M. Helmstädter, K. Lüthy, M. Gödel, M. Simons, Ashish, D. Nihalani, S. A. Rensing, K.-F. Fischbach and T. B. Huber

The BAR domain protein PICK1 regulates cell recognition and morphogenesis by interacting with Neph proteins
Molecular and Cellular Biology (MCB) (2011) M. Höhne, J. Lorscheider, A. von Bardeleben, M. Dufner, M. A. Scharf, M. Gödel, M. Helmstädter, E. M. Schurek, S. Zank, P. Gerke, C. Kurschat, S. H. Sivritas, E. Neumann-Haefelin, T. B. Huber, H. C. Reinhardt, A. C. Schauss, B. Schermer, K.-F. Fischbach and T. Benzing

aPKClambda/iota and zeta control podocyte differentiation and glomerular maturation
Journal of the American Society of Nephrology (JASN) (in press) B. Hartleben, E. Widmeier, M. Suhm, C. Schell, M. Helmstädter, T. Wiech, G. Walz, M. Leitges, M. Schiffer and T. B. Huber

Vps34 deficiency elucidates the importance of endocytosis for podocyte homeostasis
Journal of the American Society of Nephrology (JASN) (in press) W. Bechtel-Walz, M. Helmstädter, B. Hartleben, C. Schell, O. Kretz, J. Balica, F. Hrnjic, S. Liu, F. Geist, D. Kerjaschki, G. Walz and T. B. Huber

Neuronal Wiskott Aldrich Syndrome Protein (N-WASP) is required for podocyte foot process stabilization
Journal of the American Society of Nephrology (JASN) (in press) C. Schell, L. Baumhakl, S. Salou, M. Helmstädter, C. Wrede, F. Grahammer, S. Eimer, D. Kerjaschki, G. Walz, S. Snapper and T. B. Huber

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