Sendtner Lab

People

Prof. Michael Sendtner

Director, Institute of Clinical Neurobiology

sendtner_m@ukw.de

Versbacherstr.5, 97078 Würzburg

+49 931 201 44000

www.neurobiologie.uk-wuerzburg.de

Dr. Mehri Moradi

Project leader, Institute of Clinical Neurobiology

E_Moradi_M@ukw.de

Versbacherstr.5, 97078 Würzburg

+49 (931) 201-44030

www.neurobiologie.uk-wuerzburg.de

Dr. Patrick Lüningschrör

Project leader, Institute of Clinical Neurobiology

Lueningsch_P@ukw.de

Versbacherstr.5, 97078 Würzburg

+49 (931) 201-44030/28

www.neurobiologie.uk-wuerzburg.de

Dr. Stefanie Rauskolb

Project leader, Institute of Clinical Neurobiology

Rauskolb_S@ukw.de

Versbacherstr.5, 97078 Würzburg

+49 (931) 201-44008/28

www.neurobiologie.uk-wuerzburg.de

Dr. Thomas Andreska

Project leader, Institute of Clinical Neurobiology

Andreska_T@ukw.de

Versbacherstr.5, 97078 Würzburg

+49 (931) 201-44008/28

www.neurobiologie.uk-wuerzburg.de

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Publications (selected list)

Briese, M., Saal-Bauernschubert, L., Ji, C., Moradi, M., Ghanawi, H., Uhl, M., Appenzeller, S., Backofen, R., Sendtner, M. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons. PNAS 115, E2859-E2868, 2018. Doi 10.1073/pnas.1721670115

Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., Rüth von Collenberg, C., Karl, F., Damme. M., Horowitz, A., Maystadt, I., Füchtbauer, A., Füchtbauer, E.M., Jablonka, S., Blum, R., Üçeyler, N., Petri, S., Kaltschmidt, B., Jahn, R., Kaltschmidt, C., Sendtner, M. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nature Comm. 8, Art.No. 678, 2017, Doi 10.1038/s41467-017-00689-z.

Jablonka S, Sendtner M. Developmental regulation of SMN expression: pathophysiological implications and perspectives for therapy development in spinal muscular atrophy. Gene Ther. 2017 May 30. doi: 10.1038/gt.2017.46. [Epub ahead of print] Review. PubMed PMID: 28556834.

McLaughlin RL, Schijven D, van Rheenen W, van Eijk KR, O'Brien M, Kahn RS,Ophoff RA, Goris A, Bradley DG, Al-Chalabi A, van den Berg LH, Luykx JJ, Hardiman O, Veldink JH; Project MinE GWAS Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nat Commun. 2017 Mar 21;8:14774. doi:10.1038/ncomms14774. PubMed PMID: 28322246; PubMed Central PMCID: PMC5364411.

 

Moradi M, Sivadasan R, Saal L, Lüningschrör P, Dombert B, Rathod RJ, Dieterich DC, Blum R, Sendtner M. Differential roles of α-, β-, and γ-actin in axon growth and collateral branch formation in motoneurons. J Cell Biol. 2017 Mar 6;216(3):793-814. doi: 10.1083/jcb.201604117. Epub 2017 Feb 28. PubMed PMID: 28246119; PubMed Central PMCID: PMC5346967.

 

Sivadasan R, Hornburg D, Drepper C, Frank N, Jablonka S, Hansel A, Lojewski X, Sterneckert J, Hermann A, Shaw PJ, Ince PG, Mann M, Meissner F, Sendtner M. C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. Nat Neurosci. 2016 Dec;19(12):1610-1618. doi: 10.1038/nn.4407. Epub 2016 Oct 10. PubMed PMID: 27723745.

 

Jesse CM, Bushuven E, Tripathi P, Chandrasekar A, Simon CM, Drepper C, Yamoah A, Dreser A, Katona I, Johann S, Beyer C, Wagner S, Grond M, Nikolin S, Anink J, Troost D, Sendtner M, Goswami A, Weis J. ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology. Brain Pathol. 2016 Oct 28. doi: 10.1111/bpa.12453. [Epub ahead of print] PubMed PMID: 27790792.

 

Rauskolb S, Dombert B, Sendtner M. Insulin-like growth factor 1 in diabetic neuropathy and amyotrophic lateral sclerosis. Neurobiol Dis. 2017 Jan;97(Pt B):103-113. doi: 10.1016/j.nbd.2016.04.007. Epub 2016 Apr 30. Review. PubMed PMID: 27142684.

 

Yadav P, Selvaraj BT, Bender FL, Behringer M, Moradi M, Sivadasan R, Dombert B, Blum R, Asan E, Sauer M, Julien JP, Sendtner M. Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling. Acta Neuropathol. 2016 Jul;132(1):93-110. doi: 10.1007/s00401-016-1564-y. Epub 2016 Mar 28. PubMed PMID: 27021905; PubMed Central PMCID: PMC4911381.

 

Duzel E, van Praag H, Sendtner M. Can physical exercise in old age improve memory and hippocampal function? Brain. 2016 Mar;139(Pt 3):662-73. doi: 10.1093/brain/awv407. Epub 2016 Feb 11. Review. PubMed PMID: 26912638; PubMed Central PMCID: PMC4766381.  

 

Briese M, Saal L, Appenzeller S, Moradi M, Baluapuri A, Sendtner M. Whole transcriptome profiling reveals the RNA content of motor axons. Nucleic Acids Res. 2016 Feb 29;44(4):e33. doi: 10.1093/nar/gkv1027. Epub 2015 Oct 12. PubMed PMID: 26464439; PubMed Central PMCID: PMC4770199.  

 

Simon CM, Rauskolb S, Gunnersen JM, Holtmann B, Drepper C, Dombert B, Braga M, Wiese S, Jablonka S, Pühringer D, Zielasek J, Hoeflich A, Silani V, Wolf E, Kneitz S, Sommer C, Toyka KV, Sendtner M. Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy. Acta Neuropathol. 2015 Sep;130(3):373-87. doi: 10.1007/s00401-015-1446-8. Epub 2015 May 30. PubMed  PMID: 26025657; PubMed Central PMCID: PMC4541707.  

 

Hoffmann CJ, Harms U, Rex A, Szulzewsky F, Wolf SA, Grittner U, Lättig-Tünnemann G, Sendtner M, Kettenmann H, Dirnagl U, Endres M, Harms C. Vascular signal transducer and activator of transcription-3 promotes angiogenesis and neuroplasticity long-term after stroke. Circulation. 2015 May 19;131(20):1772-82. doi: 10.1161/CIRCULATIONAHA.114.013003. Epub 2015 Mar 20. PubMed PMID: 25794850.  

 

Dombert B, Sivadasan R, Simon CM, Jablonka S, Sendtner M. Presynaptic localization of Smn and hnRNP R in axon terminals of embryonic and postnatal mouse motoneurons. PLoS One. 2014 Oct 22;9(10):e110846. doi: 10.1371/journal.pone.0110846. eCollection 2014. PubMed PMID: 25338097; PubMed Central PMCID: PMC4206449.  

 

Saal L, Briese M, Kneitz S, Glinka M, Sendtner M. Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation. RNA. 2014 Nov;20(11):1789-802. doi: 10.1261/rna.047373.114. Epub 2014 Sep 22. PubMed PMID:  25246652; PubMed Central PMCID: PMC4201830. 

 

Götz R, Sendtner M. Cooperation of tyrosine kinase receptor TrkB and epidermal growth factor receptor signaling enhances migration and dispersal of lung tumor cells. PLoS One. 2014 Jun 24;9(6):e100944. doi: 10.1371/journal.pone.0100944. eCollection 2014. PubMed PMID: 24959744; PubMed Central PMCID: PMC4069166.

 

Sendtner M. Motoneuron disease. Handb Exp Pharmacol. 2014;220:411-41. doi: 10.1007/978-3-642-45106-5_15. Review. PubMed PMID: 24668481.  

 

Jablonka S, Dombert B, Asan E, Sendtner M. Mechanisms for axon maintenance and plasticity in motoneurons: alterations in motoneuron disease. J Anat. 2014 Jan;224(1):3-14. doi: 10.1111/joa.12097. Epub 2013 Sep 6. Review. PubMed PMID: 24007389; PubMed Central PMCID: PMC3867882. 

 

Selvaraj BT, Sendtner M. CNTF, STAT3 and new therapies for axonal degeneration: what are they and what can they do? Expert Rev Neurother. 2013 Mar;13(3):239-41. doi: 10.1586/ern.13.9. Review. PubMed PMID: 23448212.  

 

Puehringer D, Orel N, Lüningschrör P, Subramanian N, Herrmann T, Chao MV, Sendtner M. EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons. Nat Neurosci. 2013 Apr;16(4):407-15. doi: 10.1038/nn.3333. Epub 2013 Feb 17. PubMed PMID: 23416450; PubMed Central PMCID: PMC4148818.  

 

Selvaraj BT, Frank N, Bender FL, Asan E, Sendtner M. Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease. J Cell Biol. 2012 Oct 29;199(3):437-51. doi: 10.1083/jcb.201203109. PubMed PMID: 23109669; PubMed Central PMCID: PMC3483126.  

 

Subramanian N, Wetzel A, Dombert B, Yadav P, Havlicek S, Jablonka S, Nassar MA, Blum R, Sendtner M. Role of Na(v)1.9 in activity-dependent axon growth in motoneurons. Hum Mol Genet. 2012 Aug 15;21(16):3655-67. doi: 10.1093/hmg/dds195.  Epub 2012 May 28. PubMed PMID: 22641814.  

Research

Project 1: Neurotrophin signaling. Neurotrophic factors are essential regulators of neural plasticity. We are investigating the roles of Brain-derived neurotrophic factor (BDNF) and Ciliary neurotrophic factor (CNTF). The BDNF receptor TrkB can be transactivated by a broad spectrum of other receptors, including G-protein coupled receptors such as the adenosine type 2A receptors or other tyrosine kinase receptors such as the Epidermal growth factor Receptor (EGFR). We are interested how these factors and their receptors modulate the axonal cytoskeleton and presynaptic function in motoneurons and modulate circuits for movements and higher brain functions in the hippocampus, striatum and cerebral cortex. 

 

Project 2: Axonal protein synthesis. Motoneurons have long and highly branched axons, terminating in presynaptic compartments of neuromuscular endplates. In order to maintain these terminals, local synthesis of new proteins can take place in axons and axon terminals. We have developed techniques to identify these transcripts in cultured motoneurons and are interested to identify ribosomal structures and mechanisms for local axonal protein synthesis, using 3D Electron Tomography analyses coupled with advanced immune-lightmicroscopy, in collaboration with the groups of Markus Sauer, Christian Stigloher and Esther Asan.

 

Project 3: Dynamics of the axonal cytoskeleton. The axonal cytoskeleton is locally modulated by signaling that regulates microtubule dynamics, neurofilaments and actin dynamics. Using a combination of new mouse models, cell culture systems, advanced light microscopy and electron microscopic analyses, we collaborate with Markus Sauer and Christian Stigloher the study signaling pathways that affect actin dynamics in axons, dendrites and also the nucleus of motoneurons.

Project 4: Axonal actin dynamics. Axonal actin dynamics is severely disturbed in motoneurons from mouse models of Spinal Muscular Atrophy. At least 2 isoforms of actin-mRNA, the transcripts for α-, β- and γ actin are translocated to axons and serve different functions in axonal branch formation and in growth cone extension. We are interested in how these alterations also affect functional aspects, such as neuromuscular transmission.

Project 5: Intronic expansion in the C9orf72 gene is a common genetic cause of amyotrophic lateral sclerosis. This genetic alteration has many cellular effects, via toxic RNA transcripts and dipeptides derived from the intronic hexanucleotide expansions. In addition, transcripts for the C9orf72 gene product are reduced. We are interested in the funciton of C9ORF72 and study its cellular role in motoneurons, using mouse and human iPS cell derived culture systems and compare these effects with alterations in postmortem tissue for ALS patients.

Project 6: Axonal autophagy. Dysregulation of autophagy can contribute to neurodegeneration. We are interested in the molecular signaling mechanisms that direct synaptic vesicles and components of presynaptic active zones into autophagy, and how these mechanisms contribute to synaptic plasticity and functional maintenance at neuromuscular endplates and other types of synapses.  

© 2019 by Philip Tovote

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last update: 10/29/2019