Special Lab Molecular Biological Techniques

The formation of long-lasting memories is thought to depend on structural and functional alterations in neural networks, involving plastic rearrangements of synaptic contacts. Changes in the protein composition (proteome) of synapses are hallmarks of synaptic plasticity. The amount of a protein in synaptic structures is determined by its synthesis and degradation rates and/or by protein–protein interactions, which are mainly controlled via posttranslational protein modifications, such as phosphorylation and glycosylation.

Aim of our research is the identification and functional characterization of neurotransmitter systems, intracellular signalling pathways, and protein components forming the molecular and cellular basis of long-lasting synaptic plasticity. Special emphasis is placed on memory-relevant synaptic proteome changes and posttranslational protein modifications.

  • Head

    Head

    Karl-Heinz Smalla studied physics at the Martin-Luther University in Halle where he obtained his PhD in physical chemistry in 1983. Changing then to the Institute for Neurobiology and Brain Research in Magdeburg he turned his major research field to protein biochemistry and glycobiology of synaptic proteins which he continuously followed at several institutes with strong emphasis on neurobiological research at the Otto-von-Guericke University. Since 2001 he is working at the LIN with major focus on investigations of synaptic proteomes and their dynamics in neuroplasticity. Currently he is the head of the Special Lab Molecular Biology Techniques.

     

  • Members

    Members

    Head  
    Dr. Karl-Heinz Smalla+49-391-6263-94291smalla@lin-magdeburg.de
    Postdocs  
    Dr. Carolina Montenegro+49-391-6263-93341carolina.montenegro@lin-magdeburg.de
    Dr. Wolfgang Tischmeyer+49-391-6263-94291wolfgang.tischmeyer@lin-magdeburg.de
    Technical staff member  
    Kathrin Pohlmann+49-391-6263-94341kathrin.pohlmann@lin-magdeburg.de
    Guests  
    Dr. Patricio Orrego Lillo  
    Keisuke Yamashita  
    Alexander Engler  
    Students  
    Marie Briza  
    Hans Georg Kesseler   
    Theresa Meilfes          
    Kayatthri Thirukketeeswaran  

     

  • Projects

    Projects

    We are currently working on these questions:
     

    • Which neurotransmitters are significantly involved in discrimination learning and the formation of long-term memory?
    • Which synaptic proteins are of particular importance for learning plasticity and memory formation?
    • Which synaptic proteins are associated with neuropsychiatric diseases?
    • To what extent does the protein glycosylation have an influence on the formation of long-term memory?
    • What role do the neuronal cell adhesion molecule neuroplastin and its direct interaction partners play in synaptic plasticity?

     

  • Third Party Funds

    Third Party Funds

    2008-2019
    CRC 779 "Neurobiology of Motivated Behavior" (DFG)
    "Mechanisms of synaptic plasticity during cortex-dependent learning"
    DC Dieterich, ED Gundelfinger & W Tischmeyer (B09)
    www.sfb779.de


    2017-2019
    Scientific-Technological Cooperation with Chile (BMBF)
    "Presynaptic functions of neuroplastin - implications for endo- and exocytosis and the exocyst complex."
    KH Smalla, ED Gundelfinger, CI Seidenbecher & D Montag


    2016 - 2019
    LIN Special Project  
    "Hippocampus-dependent versus striatum-dependent spatial learning - in latent toxoplasmosis – a cross-species investigation"

  • Publications

    Publications

    2019

    Gómez-Molina C, Sandoval M, Henzi R, Ramírez JP, Varas-Godoy M, Luarte A, Lafourcade CA, Lopez-Verrilli A, Smalla K-H, Kaehne T, Wyneken U. 2019. Small extracellular vesicles in rat serum contain astrocyte-derived protein biomarkers of repetitive stress. International Journal of Neuropsychopharmacology. 22(3):232-246. https://doi.org/10.1093/ijnp/pyy098

     

    2018

    Annamneedi A, Caliskan G, Müller S, Montag D, Budinger E, Angenstein F, Fejtova A, Tischmeyer W, Gundelfinger ED, Stork O. 2018. Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance. Brain Structure and Function. 223(7):3423-3445. Available from: 10.1007/s00429-018-1692-3

    Lang D, Schott BH, van Ham M, Morton L, Kulikovskaja L, Herrera-Molina R, Pielot R, Klawonn F, Montag D, Jänsch L, Gundelfinger ED, Smalla KH, Dunay IR. 2018. Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition. Journal of Neuroinflammation. 15(1). Available from: 10.1186/s12974-018-1242-1

     

    2017

    Korthals M, Langnaese K, Smalla KH, Kähne T, Herrera-Molina R, Handschuh J, Lehmann AC, Mamula D, Naumann M, Seidenbecher C, Zuschratter W, Tedford K, Gundelfinger ED, Montag D, Fischer KD, Thomas U. 2017. A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation. Scientific Reports. 7(1). Available from: 10.1038/s41598-017-08519-4

    Herrera-Molina R, Mlinac-Jerkovic K, Ilic K, Stöber F, Vemula SK, Sandoval M, Milosevic NJ, Simic G, Smalla KH, Goldschmidt J, Bognar SK, Montag D. 2017. Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: Implication for cognitive deterioration. Scientific Reports. 7(1). Available from: 10.1038/s41598-017-07839-9

    Helbing C, Tischmeyer W, Angenstein F. 2017. Late effect of dopamine D1/5 receptor activation on stimulus-induced BOLD responses in the hippocampus and its target regions depends on the history of previous stimulations. NeuroImage. 152:119-129. Available from: 10.1016/j.neuroimage.2017.02.077

    Bhattacharya S, Herrera-Molina R, Sabanov V, Ahmed T, Iscru E, Stöber F, Richter K, Fischer KD, Angenstein F, Goldschmidt J, Beesley PW, Balschun D, Smalla KH, Gundelfinger ED, Montag D. 2017. Genetically induced retrograde amnesia of associative memories after neuroplastin ablation. Biological Psychiatry. 81(2):124-135. Available from: 10.1016/j.biopsych.2016.03.2107

    Fernández-Orth J, Ehling P, Ruck T, Pankratz S, Hofmann MS, Landgraf P, Dieterich DC, Smalla KH, Kähne T, Seebohm G, Budde T, Wiendl H, Bittner S, Meuth SG. 2017. 14-3-3 Proteins regulate K2P5.1 surface expression on T lymphocytes. Traffic. 18(1):29-43. Available from: 10.1111/tra.12455

    Leutritz T, Hilfert L, Busse U, Smalla KH, Speck O, Zhong K. 2017. Contribution of iron and protein contents from rat brain subcellular fractions to MR phase imaging. Magnetic Resonance in Medicine. 77(5):2028-2039. Available from: 10.1002/mrm.26288

     

    2016

    Kolodziej A, Smalla KH, Richter S, Engler A, Pielot R, Dieterich DC, Tischmeyer W, Naumann M, Kähne T. 2016. High resolution quantitative synaptic proteome profiling of mouse brain regions after auditory discrimination learning. Journal of Visualized Experiments. 2016(118). Available from: 10.3791/54992

    Kähne T, Richter S, Kolodziej A, Smalla KH, Pielot R, Engler A, Ohl FW, Dieterich DC, Seidenbecher C, Tischmeyer W, Naumann M, Gundelfinger ED. 2016. Proteome rearrangements after auditory learning: high-resolution profiling of synapse-enriched protein fractions from mouse brain. Journal of Neurochemistry. 124-138. Available from: 10.1111/jnc.13636

     

    2015

    Reichenbach N, Herrmann U, Kähne T, Schicknick H, Pielot R, Naumann M, Dieterich DC, Gundelfinger ED, Smalla KH, Tischmeyer W. 2015. Differential effects of dopamine signalling on long-term memory formation and consolidation in rodent brain. Proteome Science. 13(1). Available from: 10.1186/s12953-015-0069-2

     

    2014

    Beesley PW, Herrera-Molina R, Smalla KH, Seidenbecher C. 2014. The Neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function. Journal of Neurochemistry. 131(3):268-283. Available from: 10.1111/jnc.12816

    Herrera Molina R, Sarto-Jackson I, Montenegro-Venegas C, Heine M, Smalla KH, Seidenbecher CI, Beesley PW, Gundelfinger ED, Montag D. 2014. Structure of excitatory synapses and GABA<inf>a</inf> receptor localization at inhibitory synapses are regulated by neuroplastin-65. Journal of Biological Chemistry. 289(13):8973-8988. Available from: 10.1074/jbc.M113.514992

    Seidensticker M, Ulrich G, Muehlberg FL, Pethe A, Grosser OS, Steffen IG, Stiebler M, Goldschmidt J, Smalla KH, Seidensticker R, Ricke J, Amthauer H, Mohnike K. 2014. Tumor cell uptake of 99mTc-Labeled 1-Thio-β-d-glucose and 5-thio-d-glucose in comparison with 2-deoxy-2-[18 f]fluoro-d-glucose in vitro: Kinetics, dependencies, blockage and cell compartment of accumulation. Molecular Imaging and Biology. 16(2):189-198. Available from: 10.1007/s11307-013-0690-3

     

    2013

    Kemp A, Tischmeyer W, Manahan-Vaughan D. 2013. Learning-facilitated long-term depression requires activation of the immediate early gene, c-fos, and is transcription dependent. Behavioural Brain Research. 254:83-91. Available from: 10.1016/j.bbr.2013.04.036

    Li L, Sase A, Patil S, Sunyer B, Höger H, Smalla KH, Stork O, Lubec G. 2013. Distinct Set Of Kinases Induced After Retrieval of Spatial Memory Discriminate Memory Modulation Processes in the Mouse Hippocampus. Hippocampus. 23(8):672-683. Available from: 10.1002/hipo.22127

    Sandoval M, Luarte A, Herrera-Molina R, Varas-Godoy M, Santibáñez M, Rubio FJ, Smit AB, Gundelfinger ED, Li KW, Smalla KH, Wyneken U. 2013. The glycolytic enzyme aldolase C is up-regulated in rat forebrain microsomes and in the cerebrospinal fluid after repetitive fluoxetine treatment. Brain Research. 1520:1-14. Available from: 10.1016/j.brainres.2013.04.049

    Leutritz T, Hilfert L, Smalla KH, Speck O, Zhong K. 2013. Accurate quantification of water-macromolecule exchange induced frequency shift: Effects of reference substance. Magnetic Resonance in Medicine. 69(1):263-268. Available from: 10.1002/mrm.24223

    Smalla KH, Klemmer P, Wyneken U. 2013. Isolation of the postsynaptic density: A specialization of the subsynaptic cytoskeleton. In Neuromethods. pp. 265-280. (Neuromethods). Available from: 10.1007/978-1-62703-266-7-11

     

    2012

    Bernstein HG, Smalla KH, Dürrschmidt D, Keilhoff G, Dobrowolny H, Steiner J, Schmitt A, Kreutz MR, Bogerts B. 2012. Increased density of prohibitin-immunoreactive oligodendrocytes in the dorsolateral prefrontal white matter of subjects with schizophrenia suggests extraneuronal roles for the protein in the disease. NeuroMolecular Medicine. 14(4):270-280. Available from: 10.1007/s12017-012-8185-y

    Mlinac K, Jovanov Milošević N, Heffer M, Smalla KH, Schnaar RL, Kalanj Bognar S. 2012. Neuroplastin expression in the hippocampus of mice lacking complex gangliosides. Journal of Molecular Neuroscience. 48(1):161-166. Available from: 10.1007/s12031-012-9801-x

    Hodas JJL, Nehring A, Höche N, Sweredoski MJ, Pielot R, Hess S, Tirrell DA, Dieterich DC, Schuman EM. 2012. Dopaminergic modulation of the hippocampal neuropil proteome identified by bioorthogonal noncanonical amino acid tagging (BONCAT). Proteomics. 12(15-16):2464-2476. Available from: 10.1002/pmic.201200112

    Kähne T, Kolodziej A, Smalla KH, Eisenschmidt E, Haus UU, Weismantel R, Kropf S, Wetzel W, Ohl FW, Tischmeyer W, Naumann M, Gundelfinger ED. 2012. Synaptic proteome changes in mouse brain regions upon auditory discrimination learning. Proteomics. 12(15-16):2433-2444. Available from: 10.1002/pmic.201100669

    Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV, Kuebler A, Janssen AL, Udvardi PT, Shiban E, Spilker C, Balschun D, Skryabin BV, Dieck ST, Smalla KH, Montag D, Leblond CS, Faure P, Torquet N, Le Sourd AM, Toro R, Grabrucker AM, Shoichet SA, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger ED, Boeckers TM. 2012. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature. 486(7402):256-260. Available from: 10.1038/nature11015

    Sarto-Jackson I, Milenkovic I, Smalla KH, Gundelfinger ED, Kaehne T, Herrera-Molina R, Thomas S, Kiebler MA, Sieghart W. 2012. The cell adhesion molecule neuroplastin-65 is a novel interaction partner of γ-aminobutyric acid type A receptors. Journal of Biological Chemistry. 287(17):14201-14214. Available from: 10.1074/jbc.M111.293175

    Schicknick H, Reichenbach N, Smalla KH, Scheich H, Gundelfinger ED, Tischmeyer W. 2012. Dopamine modulates memory consolidation of discrimination learning in the auditory cortex. European Journal of Neuroscience. 35(5):763-774. Available from: 10.1111/j.1460-9568.2012.07994.x

    Pielot R, Smalla KH, Müller A, Landgraf P, Lehmann AC, Eisenschmidt E, Haus UU, Weismantel R, Gundelfinger ED, Dieterich DC. 2012. Synprot: A database for proteins of detergent-resistant synaptic protein preparations. Frontiers in Synaptic Neuroscience. (JUN). Available from: 10.3389/fnsyn.2012.00001

     

    2011

    Sandoval R, González A, Caviedes A, Pancetti F, Smalla KH, Kaehne T, Michea L, Gundelfinger ED, Wyneken U. 2011. Homeostatic NMDA receptor down-regulation via brain derived neurotrophic factor and nitric oxide-dependent signalling in cortical but not in hippocampal neurons. Journal of Neurochemistry. 118(5):760-772. Available from: 10.1111/j.1471-4159.2011.07365.x

    Scheich H, Brechmann A, Brosch M, Budinger E, Ohl FW, Selezneva E, Stark H, Tischmeyer W, Wetzel W. 2011. Behavioral semantics of learning and crossmodal processing in auditory cortex: The semantic processor concept. Hearing Research. 271(1-2):3-15. Available from: 10.1016/j.heares.2010.10.006

    Smalla KH, Wyneken U. 2011. Two-dimensional gel electrophoresis-based proteomic analysis of brain synapses. In Neuromethods. pp. 95-113. (Neuromethods). Available from: 10.1007/978-1-61779-111-6_8

     

    2010

    Goswami C, Rademacher N, Smalla KH, Kalscheuer V, Ropers HH, Gundelfinger ED, Hucho T. 2010. TRPV1 acts as a synaptic protein and regulates vesicle recycling. Journal of Cell Science. 123(12):2045-2057. Available from: 10.1242/jcs.065144

    Dürrschmidt D, Smalla KH, Kreutz MR, Dobrowolny H, Steiner J, Keilhoff G, Bogerts B, Bernstein HG. 2010. Increased oligodendroglial expression of the cell proliferation?controlling protein prohibitin in schizophrenia. A hint for cell cycle abnormalities?. Acta Clinica Croatica. 49(SUPPL. 2):39-41.

  • Teaching & Internships

    Teaching & Internships

    We are involved in the education of students of the master's program "Integrative Neuroscience". Members of our group teach in the course "Neural Signalling" and we offer internships in "Protein-Protein Interaction Studies" and "Synaptoproteomics".

     

    With the support of the Neuroscience Society in Germany, we have already offered several one-week courses in "SynaptoProteomics" with international participation.


    Furthermore, there are opportunities for students from foreign universities:

    • Internship semester
    • Lab visits for work with the aim of writing a bachelor's or master's thesis
    • Stays within the framework of the Erasmus exchange programme or the DAAD


    We also try to make student internships possible.

     

  • Methods

    Methods

    Standard protein biochemical methods
    (e.g. tissue fractionation, protein precipitation, protein determinations)


    Production and purification of recombinant proteins
    (in bacteria or in eukaryotic cell lines)


    Protein biochemical separation processes

    • Subcellular fractionations (membrane fractions, synapse fractions, post-synaptic densities, cell nuclei)
    • Electrophoretic separation methods (SDS gel electrophoresis, isoelectric focusing, blue native electrophoresis, two-dimensional gel electrophoresis)
    • Chromatographic separation methods (HPLC, ÄKTA): gel filtration, ion exchange chromatography, reverse phase chromatography, affinity chromatography
    • Pull Down
       

    Immunochemical processes

    • immunoblotting
    • immunoprecipitation   
    • ELISA
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