@article{AndreskaLueningschroerSendtner2020,
  author    = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Sendtner, Michael},
  title     = {Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor},
  series = {Cell and Tissue Research},
  volume    = {382},
  journal   = {Cell and Tissue Research},
  doi       = {10.1007/s00441-020-03224-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235055},
  pages     = {5-14},
  year      = {2020},
  abstract  = {Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.},
  language  = {en}
}
@article{BrieseSaalBauernschubertLueningschroeretal.2020,
  author    = {Briese, Michael and Saal-Bauernschubert, Lena and L{\"u}ningschr{\"o}r, Patrick and Moradi, Mehri and Dombert, Benjamin and Surrey, Verena and Appenzeller, Silke and Deng, Chunchu and Jablonka, Sibylle and Sendtner, Michael},
  title     = {Loss of Tdp-43 disrupts the axonal transcriptome of motoneurons accompanied by impaired axonal translation and mitochondria function},
  series = {Acta Neuropathologica Communications},
  volume    = {8},
  journal   = {Acta Neuropathologica Communications},
  doi       = {10.1186/s40478-020-00987-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230322},
  year      = {2020},
  abstract  = {Protein inclusions containing the RNA-binding protein TDP-43 are a pathological hallmark of amyotrophic lateral sclerosis and other neurodegenerative disorders. The loss of TDP-43 function that is associated with these inclusions affects post-transcriptional processing of RNAs in multiple ways including pre-mRNA splicing, nucleocytoplasmic transport, modulation of mRNA stability and translation. In contrast, less is known about the role of TDP-43 in axonal RNA metabolism in motoneurons. Here we show that depletion of Tdp-43 in primary motoneurons affects axon growth. This defect is accompanied by subcellular transcriptome alterations in the axonal and somatodendritic compartment. The axonal localization of transcripts encoding components of the cytoskeleton, the translational machinery and transcripts involved in mitochondrial energy metabolism were particularly affected by loss of Tdp-43. Accordingly, we observed reduced protein synthesis and disturbed mitochondrial functions in axons of Tdp-43-depleted motoneurons. Treatment with nicotinamide rescued the axon growth defect associated with loss of Tdp-43. These results show that Tdp-43 depletion in motoneurons affects several pathways integral to axon health indicating that loss of TDP-43 function could thus make a major contribution to axonal pathomechanisms in ALS.},
  language  = {en}
}
@article{LueningschroerSlottaHeimannetal.2020,
  author    = {L{\"u}ningschr{\"o}r, Patrick and Slotta, Carsten and Heimann, Peter and Briese, Michael and Weikert, Ulrich M. and Massih, Bita and Appenzeller, Silke and Sendtner, Michael and Kaltschmidt, Christian and Kaltschmidt, Barbara},
  title     = {Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2020.00185},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207538},
  year      = {2020},
  abstract  = {Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4\(^+\) and CD8\(^+\) T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.},
  language  = {en}
}
@article{LueningschroerBinottiDombertetal.2017,
  author    = {L{\"u}ningschr{\"o}r, Patrick and Binotti, Beyenech and Dombert, Benjamin and Heimann, Peter and Perez-Lara, Angel and Slotta, Carsten and Thau-Habermann, Nadine and von Collenberg, Cora R. and Karl, Franziska and Damme, Markus and Horowitz, Arie and Maystadt, Isabelle and F{\"u}chtbauer, Annette and F{\"u}chtbauer, Ernst-Martin and Jablonka, Sibylle and Blum, Robert and {\"U}{\c{c}}eyler, Nurcan and Petri, Susanne and Kaltschmidt, Barbara and Jahn, Reinhard and Kaltschmidt, Christian and Sendtner, Michael},
  title     = {Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease},
  series = {Nature Communications},
  volume    = {8},
  journal   = {Nature Communications},
  number    = {678},
  doi       = {10.1038/s41467-017-00689-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170048},
  year      = {2017},
  abstract  = {Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.},
  language  = {en}
}
@article{DombertBalkLueningschroeretal.2017,
  author    = {Dombert, Benjamin and Balk, Stefanie and L{\"u}ningschr{\"o}r, Patrick and Moradi, Mehri and Sivadasan, Rajeeve and Saal-Bauernschubert, Lena and Jablonka, Sibylle},
  title     = {BDNF/trkB induction of calcium transients through Ca\(_{v}\)2.2 calcium channels in motoneurons corresponds to F-actin assembly and growth cone formation on β2-chain laminin (221)},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Molecular Neuroscience},
  number    = {346},
  doi       = {10.3389/fnmol.2017.00346},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159094},
  year      = {2017},
  abstract  = {Spontaneous Ca\(^{2+}\) transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca\(^{2+}\) influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation. Primary motoneurons from mouse embryos were cultured on the synapse specific, β2-chain containing laminin isoform (221) regulating axon elongation through spontaneous Ca\(^{2+}\) transients that are in turn induced by enhanced clustering of N-type specific voltage-gated Ca\(^{2+}\) channels (Ca\(_{v}\)2.2) in axonal growth cones. TrkB-deficient (trkBTK\(^{-/-}\)) mouse motoneurons which express no full-length trkB receptor and wildtype motoneurons cultured without BDNF exhibited reduced spontaneous Ca\(^{2+}\) transients that corresponded to altered axon elongation and defects in growth cone morphology which was accompanied by changes in the local actin cytoskeleton. Vice versa, the acute application of BDNF resulted in the induction of spontaneous Ca\(^{2+}\) transients and Ca\(_{v}\)2.2 clustering in motor growth cones, as well as the activation of trkB downstream signaling cascades which promoted the stabilization of β-actin via the LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we identified a mutual regulation of neuronal excitability and actin dynamics in axonal growth cones of embryonic motoneurons cultured on laminin-221/211. Impaired excitability resulted in dysregulated axon extension and local actin cytoskeleton, whereas upon β-actin knockdown Ca\(_{v}\)2.2 clustering was affected. We conclude from our data that in embryonic motoneurons BDNF/trkB signaling contributes to axon elongation and growth cone formation through changes in the local actin cytoskeleton accompanied by increased Ca\(_{v}\)2.2 clustering and local calcium transients. These findings may help to explore cellular mechanisms which might be dysregulated during maturation of embryonic motoneurons leading to motoneuron disease.},
  language  = {en}
}