TY  - JOUR
A1  - Schmitt, Dominique
A1  - Funk, Natalia
A1  - Blum, Robert
A1  - Asan, Esther
A1  - Andersen, Lill
A1  - Rülicke, Thomas
A1  - Sendtner, Michael
A1  - Buchner, Erich
T1  - Initial characterization of a Syap1 knock-out mouse and distribution of Syap1 in mouse brain and cultured motoneurons
JF  - Histochemistry and Cell Biology
N2  - Synapse-associated protein 1 (Syap1/BSTA) is the mammalian homologue of Sap47 (synapse-associated protein of 47 kDa) in Drosophila. Sap47 null mutant larvae show reduced short-term synaptic plasticity and a defect in associative behavioral plasticity. In cultured adipocytes, Syap1 functions as part of a complex that phosphorylates protein kinase B alpha/Akt1 (Akt1) at Ser\(^{473}\) and promotes differentiation. The role of Syap1 in the vertebrate nervous system is unknown. Here, we generated a Syap1 knock-out mouse and show that lack of Syap1 is compatible with viability and fertility. Adult knock-out mice show no overt defects in brain morphology. In wild-type brain, Syap1 is found widely distributed in synaptic neuropil, notably in regions rich in glutamatergic synapses, but also in perinuclear structures associated with the Golgi apparatus of specific groups of neuronal cell bodies. In cultured motoneurons, Syap1 is located in axons and growth cones and is enriched in a perinuclear region partially overlapping with Golgi markers. We studied in detail the influence of Syap1 knockdown and knockout on structure and development of these cells. Importantly, Syap1 knockout does not affect motoneuron survival or axon growth. Unexpectedly, neither knockdown nor knockout of Syap1 in cultured motoneurons is associated with reduced Ser\(^{473}\) or Thr\(^{308}\) phosphorylation of Akt. Our findings demonstrate a widespread expression of Syap1 in the mouse central nervous system with regionally specific distribution patterns as illustrated in particular for olfactory bulb, hippocampus, and cerebellum.
KW  - Protein kinase B
KW  - Spinal Muscular-arthropy
KW  - Rictor-mTOR complex
KW  - Neurotrophic factors
KW  - Plasma-membrane
KW  - Axon growth
KW  - SAP47 gene
KW  - Phosphorylation
KW  - Drosophilia
KW  - Cells
KW  - BSTA
KW  - Viability
KW  - Brain
KW  - Syap1 localization
KW  - Glutamatergic synapses
KW  - PKB/Akt phosphorylation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187258
VL  - 146
IS  - 4
ER  - 
TY  - JOUR
A1  - Ghanawi, Hanaa
A1  - Hennlein, Luisa
A1  - Zare, Abdolhossein
A1  - Bader, Jakob
A1  - Salehi, Saeede
A1  - Hornburg, Daniel
A1  - Ji, Changhe
A1  - Sivadasan, Rajeeve
A1  - Drepper, Carsten
A1  - Meissner, Felix
A1  - Mann, Matthias
A1  - Jablonka, Sibylle
A1  - Briese, Michael
A1  - Sendtner, Michael
T1  - Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin
JF  - Nucleic Acids Research
N2  - Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stress. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing giving rise to a full-length protein and a shorter isoform lacking its N-terminal acidic domain. To investigate functions selectively associated with the full-length hnRNP R isoform, we generated a Hnrnpr knockout mouse (Hnrnpr\(^{tm1a/tm1a}\)) in which expression of full-length hnRNP R was abolished while production of the truncated hnRNP R isoform was retained. Motoneurons cultured from Hnrnpr\(^{tm1a/tm1a}\) mice did not show any axonal growth defects but exhibited enhanced accumulation of double-strand breaks and an impaired DNA damage response upon exposure to genotoxic agents. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1-depleted motoneurons were defective in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage where it interacts with gamma-H2AX, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its N-terminal acidic domain in this context.
KW  - nuclear ribonucleoprotein-R
KW  - determining gene-product
KW  - actin messenger RNA
KW  - comet assay
KW  - genome wide
KW  - spinal cord
KW  - YB-1
KW  - SMN
KW  - interacts
KW  - enrichment
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265687
VL  - 49
IS  - 21
ER  -