Bio

Honors & Awards


  • PhD Thesis Award, BFB (2006)

Education & Certifications


  • Ph.D., University of Bonn, Molecular Genetics (2005)
  • Dipl.-Biol. (M.Sc.), University of Bonn, Biology (2000)

Publications

Journal Articles


  • Latrophilins Function as Heterophilic Cell-adhesion Molecules by Binding to Teneurins: REGULATION BY ALTERNATIVE SPLICING. The Journal of biological chemistry Boucard, A. A., Maxeiner, S., Südhof, T. C. 2014; 289 (1): 387-402

    Abstract

    Latrophilin-1, -2, and -3 are adhesion-type G protein-coupled receptors that are auxiliary α-latrotoxin receptors, suggesting that they may have a synaptic function. Using pulldowns, we here identify teneurins, type II transmembrane proteins that are also candidate synaptic cell-adhesion molecules, as interactors for the lectin-like domain of latrophilins. We show that teneurin binds to latrophilins with nanomolar affinity and that this binding mediates cell adhesion, consistent with a role of teneurin binding to latrophilins in trans-synaptic interactions. All latrophilins are subject to alternative splicing at an N-terminal site; in latrophilin-1, this alternative splicing modulates teneurin binding but has no effect on binding of latrophilin-1 to another ligand, FLRT3. Addition to cultured neurons of soluble teneurin-binding fragments of latrophilin-1 decreased synapse density, suggesting that latrophilin binding to teneurin may directly or indirectly influence synapse formation and/or maintenance. These observations are potentially intriguing in view of the proposed role for Drosophila teneurins in determining synapse specificity. However, teneurins in Drosophila were suggested to act as homophilic cell-adhesion molecules, whereas our findings suggest a heterophilic interaction mechanism. Thus, we tested whether mammalian teneurins also are homophilic cell-adhesion molecules, in addition to binding to latrophilins as heterophilic cell-adhesion molecules. Strikingly, we find that although teneurins bind to each other in solution, homophilic teneurin-teneurin binding is unable to support stable cell adhesion, different from heterophilic teneurin-latrophilin binding. Thus, mammalian teneurins act as heterophilic cell-adhesion molecules that may be involved in trans-neuronal interaction processes such as synapse formation or maintenance.

    View details for DOI 10.1074/jbc.M113.504779

    View details for PubMedID 24273166

  • The molecular basis of the specificity and cross-reactivity of the NeuN epitope of the neuron-specific splicing regulator, Rbfox3. Histochemistry and cell biology Maxeiner, S., Glassmann, A., Kao, H. T., Schilling, K. 2014; 141 (1): 43-55

    Abstract

    Ever since its description and the generation of its defining antibody, some 20 years ago, neural nuclei (NeuN) have been an invaluable tool for developmental neuroscientists and neuropathologists to identify neurons and follow their normal or malignant development. The recent identification of the splicing factor Rbfox3 as the molecule constituting the genuine NeuN epitope has opened up a novel perspective on NeuN immunostaining and its interpretation. Here, we briefly review these recent developments, and we provide a series of data that allow to rationalize the specificity of the NeuN/A60 antibody on aldehyde-fixed tissues on the one hand, and its cross-reactivity with Synapsin I and R3hdm2 on Western blots on the other. We argue that rather than being considered as a mere marker for mature neurons, Rbfox3-mediated NeuN/A60 immunoreactivity may provide a window onto neuronal biology. Specifically, we hypothesize that the phosphorylation-dependent antigenicity of the Rbfox3/NeuN epitope should allow to visualize neuronal physiology realized through Rbfox3, including splicing, on the single-cell level.

    View details for DOI 10.1007/s00418-013-1159-9

    View details for PubMedID 24150744

  • Localization of neurones expressing the gap junction protein Connexin45 within the adult spinal dorsal horn: a study using Cx45-eGFP reporter mice Brain Struct Funct Chapman RJ, Lall VK, Maxeiner S, Willecke K, Deuchars J, King AE 2012
  • Residual Cx45 and its relationship to Cx43 in Murine ventricular myocardium CHANNELS Bao, M., Kanter, E. M., Huang, R. Y., Maxeiner, S., Frank, M., Zhang, Y., Schuessler, R. B., Smith, T. W., Townsend, R. R., Rohrs, H. W., Berthoud, V. M., Willecke, K., Laing, J. G., Yamada, K. A. 2011; 5 (6): 489-499

    Abstract

    Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane sections, electrophysiological recordings to whole hearts, and high-resolution tandem mass spectrometry to Cx45 fusion protein, and developed two new tools, anti-Cx45 antisera and Cre(+);Cx45 floxed mice, to facilitate characterization of Cx45 in adult mammalian hearts. We found that Cx45 represents 0.3% of total Cx protein (predominantly 200 fmol Cx43 protein/?g ventricular protein) and colocalizes with Cx43 in native ventricular gap junctions, particularly in the apex and septum. Cre(+);Cx45 floxed mice express 85% less Cx45, but do not exhibit overt electrophysiologic abnormalities. Although the basal phosphorylation status of native Cx45 remains unknown, CaMKII phosphorylates 8 Ser/Thr residues in Cx45 in vitro. Thus, although downregulation of Cx45 does not produce notable deficits in electrical conduction in adult, disease-free hearts, Cx45 is a target of the multifunctional kinase CaMKII, and the phosphorylation status of Cx45 and the role of Cx43/Cx45 heteromeric gap junction channels in both normal and diseased hearts merits further investigation.

    View details for DOI 10.4161/chan.5.6.18523

    View details for Web of Science ID 000300153700008

    View details for PubMedID 22127232

  • The role of neuronal connexins 36 and 45 in shaping spontaneous firing patterns in the developing retina J Neurosci Blankenship A, Hamby A, Firl A, Vyas S, Maxeiner S, Willecke K, Feller MB 2011; 31 (27): 9998-10008
  • Deletion of connexin45 in mouse neurons disrupts one-trial object recognition and alters kainate-induced gamma-oscillations in the hippocampus Physiol Behav Zlomuzica A, Reichinnek S, Maxeiner S, Both M, May E, Wörsdörfer P, Draguhn A, Willecke K, Dere E. 2010; 101 (2): 245-53
  • A novel type of interplexiform amacrine cell in the mouse retina Eur J Neurosci Dedek K, B., Pérez de Sevilla-Müller, Maxeiner S, Schultz K, Janssen-Bienhold U, Willecke K, Euler T, Weiler R 2009; 30: 217-228
  • Connexin expression and functional analysis of gap junctional communication in mouse embryonic stem cells Stem Cells Wörsdörfer P, Maxeiner S, Markopoulos C, Kirfel G, Wulf V, Auth T, Urschel S, von Maltzahn J, Willecke K. 2008; 26 (2): 431-9
  • Connexin45 is expressed in the juxtaglomerular apparatus and is involved in the regulation of renin secretion and blood pressure Am J Physiol Regul Integr Comp Physiol. Hanner F, von Maltzahn J, Maxeiner S, Toma I, Sipos A, Kr_ger O, Willecke K, Peti-Peterdi J. 2008; 295 (2): R371-80
  • Unusually rapid evolution of Neuroligin-4 in mice. Proc Natl Acad Sci U S A Bolliger MF, Pei J, Maxeiner S, Boucard AA, Grishin NV, S_dhof TC. 2008; 105 (17): 6421-6
  • Localization of heterotypic gap junctions composed of connexin45 and connexin36 in the rod pathway of the mouse retina EUROPEAN JOURNAL OF NEUROSCIENCE Dedek, K., Schultz, K., Pieper, M., Dirks, P., Maxeiner, S., Willecke, K., Weiler, R., Janssen-Bienhold, U. 2006; 24 (6): 1675-1686

    Abstract

    The primary rod pathway in mammals contains gap junctions between AII amacrine cells and ON cone bipolar cells which relay the rod signal into the cone pathway under scotopic conditions. Two gap junctional proteins, connexin36 (Cx36) and connexin45 (Cx45), appear to play a pivotal role in this pathway because lack of either protein leads to an impairment of visual transmission under scotopic conditions. To investigate whether these connexins form heterotypic gap junctions between ON cone bipolar and AII amacrine cells, we used newly developed Cx45 antibodies and studied the cellular and subcellular distribution of this protein in the mouse retina. Specificity of the Cx45 antibodies was determined, among others, by Western blot and immunostaining of mouse heart, where Cx45 is abundantly expressed. In mouse retina, Cx45 immunosignals were detected in both plexiform layers and the ganglion cell layer. Double staining for Cx45 and Cx36 revealed a partial overlap in the punctate patterns in the ON sublamina of the inner plexiform layer of the retina. We quantified the distributions of these two connexins in the ON sublamina, and detected 30% of the Cx45 signals to be co-localized with or in close apposition to Cx36 signals. Combining immunostaining and intracellular dye injection revealed an overlap or tight association of Cx36 and Cx45 signals on the terminals of injected AII amacrine and two types of ON cone bipolar cells. Our results provide direct evidence for heterotypic gap junctions composed of Cx36 and Cx45 between AII amacrine and certain types of ON cone bipolar cells.

    View details for DOI 10.1111/j.1460-9568.2006.05052.x

    View details for Web of Science ID 000240660800017

    View details for PubMedID 17004931

  • Spatiotemporal distribution of Connexin45 in the olivocerebellar system JOURNAL OF COMPARATIVE NEUROLOGY Van Der Giessen, R. S., Maxeiner, S., French, P. J., WILLECKE, K., De Zeeuw, C. I. 2006; 495 (2): 173-184

    Abstract

    The olivocerebellar system is involved in the transmission of information to maintain sensory motor coordination. Gap junctions have been described in various types of neurons in this system, including the neurons in the inferior olive that provide the climbing fibers to Purkinje cells. While it is well established that Connexin36 is necessary for the formation of these neuronal gap junctions, it is not clear whether these electrical synapses can develop without Connexin45. Here we describe the development and spatiotemporal distribution of Connexin45 in relation to that of Connexin36 in the olivocerebellar system. During development Connexin45 is expressed in virtually all neurons of the inferior olive and cerebellar nuclei. During later postnatal development and adulthood there is a considerable overlap of expression of both connexins in subpopulations of all main olivary nuclei and cerebellar nuclei as well as in the stellate cells in the cerebellar cortex. Despite this prominent expression of Connexin45, ultrastructural analysis of neuronal gap junctions in null-mutants of Connexin45 showed that their formation appears normal in contrast to that in knockouts of Connexin36. These morphological data suggest that Connexin45 may play a modifying role in widely distributed, coupled neurons of the olivocerebellar system, but that it is not essential for the creation of its neuronal gap junctions.

    View details for DOI 10.1002/cne.20873

    View details for Web of Science ID 000235567200002

    View details for PubMedID 16435305

  • Cardiac morphogenetic defects and conduction abnormalities in mice homozygously deficient for connexin40 and heterozygously deficient for connexin45. J Mol Cell Cardiol Kr_ger O, Maxeiner S, Kim JS, van Rijen HV, de Bakker JM, Eckardt D, Tiemann K, Lewalter T, Ghanem A, L_deritz B, Willecke K. 2006; 41 (5): 787-97
  • Expression and functions of neuronal gap junctions Nat Rev Neurosci Söhl G, Maxeiner S, Willecke K 2005; 6 (3): 191-200
  • Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43 J Cell Sci Araya R, Eckardt D, Maxeiner S, Kr_ger O, Theis M, Willecke K, Sez JC 2005; 118 (Pt 1): 27-37
  • Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impaired visual transmission J Neurosci Maxeiner S, Dedek K, Janssen-Bienhold U, Ammerm_ller J, Brune H, Kirsch T, Pieper M, Degen J, Kr_ger O, Willecke 2005; 25 (3): 566-76
  • Connexin45 mediates gap junctional coupling of bistratified ganglion cells in the mouse retina J Comp Neurol Schubert T, Maxeiner S, Kr_ger O, Willecke K, Weiler R 2005; 490 (1): 29-39
  • Expression of the connexin43- and connexin45-encoding genes in the developing and mature mouse inner ear Cell Tissue Res Cohen-Salmon M, Maxeiner S, Kr_ger O, Theis M, Willecke K, Petit C 2004; 316 (1): 15-22
  • New insights into the expression and function of neural connexins with transgenic mouse mutants Brain Res Brain Res Rev Söhl G, Odermatt B, Maxeiner S, Degen J, Willecke K 2004; 47 (1-3): 245-59
  • Spatiotemporal transcription of connexin45 during brain development results in neuronal expression in adult mice Neuroscience Maxeiner S, Kr_ger O, Schilling K, Traub O, Urschel S, Willecke K 2003; 119 (3): 689-700
  • Defective vascular development in connexin 45-deficient mice Development Kr_ger O, Plum A, Kim JS, Winterhager E, Maxeiner S, Hallas G, Kirchhoff S, Traub O, Lamers WH, Willecke K 2000; 127 (19): 4179-93

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