Forschung

Papadopoulos S, Tinschert R, Papadopoulos I, Gerloff X, Schmitz F. (2024)

Analytical Post-Embedding Immunogold-Electron Microscopy with Direct Gold-Labelled Monoclonal Primary Antibodies against RIBEYE A- and B-Domain Suggests a Refined Model of Synaptic Ribbon Assembly.

Int. J. Mol. Sci. 2024, 25(13), 7443;

 https://doi.org/10.3390/ijms25137443
 

Martus D, Williams SK, Pichi K, Mannebach-Götz S, Kaiser N, Wardas B, Fecher-Trost C, Meyer MR, Schmitz F, Beck A, Fairless R, Diem R, Flockerzi V, Belkacemi A (2024)Cavβ3 Contributes to the Maintenance of the Blood-Brain Barrier and Alleviates Symptoms of Experimental Autoimmune Encephalitis.

Arterioscler Thromb Vasc Biol. 2024 Jul 3. 

https://www.ahajournals.org/doi/10.1161/ATVBAHA.124.321141
 

Suiwal S, Wartenberg P, Boehm U, Schmitz F, Schwarz K (2024)

A novel Cre recombinase mouse strain for cell-specific deletion of floxed genes in ribbon synapse-forming retinal neurons.

Int. J. Mol. Sci. 2024, 25(3), 1916

https://www.mdpi.com/1422-0067/25/3/1916

Dittrich A, Ramesh G, Jung M, Schmitz F (2023) 

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Cells 12(12), 1665.

https://www.mdpi.com/2073-4409/12/12/1665

Schwarz K, Schmitz F (2023)   

Synapse dysfunctions in multiple sclerosis

Int. J. Mol. Sci. 24(2), 1639.

https://www.mdpi.com/1422-0067/24/2/1639

Suiwal S, Dembla M, Schwarz K, Katiyar R, Jung M, Carius Y, Maxeiner S, Lauterbach MA, Lancaster CRD, Schmitz F.

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses.

International Journal of Molecular Sciences. 2022; 23(13):7135.

https://doi.org/10.3390/ijms23137135

Shankhwar S, Schwarz K, Katiyar R, Jung M, Maxeiner S, Südhof TC, Schmitz F (2022)

RIBEYE B-Domain Is Essential for RIBEYE A-Domain Stability and Assembly of Synaptic Ribbons

Frontiers in Molecular Neuroscience 15, 838311

https://www.frontiersin.org/articles/10.3389/fnmol.2022.838311/full

Mukherjee A, Katiyar R, Dembla E, Dembla M, Kumar P, Belkacemi A, Jung M, Beck A, Flockerzi V, Schwarz K, Schmitz F (2020)
Disturbed presynaptic Ca²⁺ signaling in photoreceptors in the EAE mouse model of multiple sclerosis

iScience 23(12), 101830

DOI:https://doi.org/10.1016/j.isci.2020.101830

https://www.mdpi.com/1422-0067/22/19/10789

Kesharwani A, Schwarz K, Dembla E, Dembla M, Schmitz F (2021)
Early Changes in Exo- and Endocytosis in the EAE Mouse model of multiple sclerosis correlate with decreased synaptic ribbon size and reduced ribbon-associated vesicle pools in rod photoreceptor synapses

Int. J. Mol. Sci, 221, 789.

https://www.mdpi.com/journal/ijms/special_issues/ribbon_synapses

Fairless R, Williams SK, Katiyar R, Maxeiner S, Schmitz F, Diem R. (2020)
ERG responses in mice with deletion of the synaptic ribbon component RIBEYE

Invest Ophthalmol Vis Sci. 2020 May 11;61(5):37. doi: 10.1167/iovs.61.5.37.

https://iovs.arvojournals.org/article.aspx?articleid=2766228

Dembla E, Dembla M, Maxeiner S, Schmitz F (2020)
Synaptic ribbons foster active zone stability and illumination-dependent active zone enrichment of RIM2 and Cav1.4 in photoreceptor synapses

Scientific reports 10, 5957 (2020)

https://www.nature.com/articles/s41598-020-62734-0

Moser T, Grabner CP, Schmitz F (2019)

Sensory processing at ribbon synapses in the retina and the cochlea

Physiol Rev. 100(1),103-144

https://www.physiology.org/doi/abs/10.1152/physrev.00026.2018

Okawa H, Yu WQ, Matti U, Schwarz K, Odermatt B, Zhong H, Tsukamoto Y, Lagnado L, Rieke F, Schmitz F, Wong RO (2019)

Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system.

Nature Communications (2019) 10, 2167;  10.1038/s41467-019-10123-1

https://www.nature.com/articles/s41467-019-10123-1#Ack1

Favaro PD, Huang X, Hosang L, Stodieck S, Cui L, Liu YZ, Engelhardt KA, Schmitz F, Dong Y, Löwel S, Schlüter OM (2018)

An opposing function in paralogs in balancing developmental synapse maturation

PLoS Biol. 2018 Dec 26;16(12):e2006838. doi: 10.1371/journal.pbio.2006838.

https://www.ncbi.nlm.nih.gov/pubmed/30586380

Yu WQ, El-Danaf RN, Okawa H, Pacholec JM, Matti U, Schwarz K, Odermatt B, Dunn FA, Lagnado L, Schmitz F, Huberman AD, Wong ROL (2018)

Synaptic convergence patterns onto retinal ganglion cells are preserved despite topographic variation in pre- and postsynaptic territories.

Cell Rep.25, 2017-2026

https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31693-0

Mayur Dembla, Ajay Kesharwani, Sivaraman Natarajan, Claudia Fecher‐Trost, Richard Fairless, Sarah K Williams, Veit Flockerzi, Ricarda Diem, Karin Schwarz, Frank Schmitz (2018)

Early auto‐immune targeting of photoreceptor ribbon synapses in mouse models of multiple sclerosis

EMBO Molecular Medicine e8926 DOI 10.15252/emmm.201808926 | Published online 28.09.2018

http://embomolmed.embopress.org/content/early/2018/09/28/emmm.201808926

Schwarz K, Schmitz F (2017)

Dysfunctional neuronal synapses in multiple sclerosis

Current Trends in Neurology 11, 1-13

http://www.researchtrends.net/tia/title_issue.asp?id=47&in=0&vn=11&type=3

Eich ML*, Dembla E*, Wahl S, Dembla M, Schwarz K, Schmitz F* (2017)

The calcineurin-binding, activity-dependent splice variant dynamin1xb is highly enriched in synapses in various regions of the central nervous system.

Frontiers in Molecular Neuroscience 10, 230.

http://journal.frontiersin.org/article/10.3389/fnmol.2017.00230/full

Karin Schwarz, Frank Schmitz (2017)

RIBEYE(B)-domain binds to lipid components of synaptic vesicles in an NAD(H)-dependent, redox-sensitive manner.

Biochem. J., epub ahead of print. pii: BCJ20160886. doi: 10.1042/BCJ20160886.

https://www.ncbi.nlm.nih.gov/pubmed/28202712

Shweta Suiwal, Gabriele Kiefer, Frank Schmitz, Karin Schwarz (2017)

An easy, fast and “low-tech”-equipment-requiring alternative method to optimize immunolabelling conditions for pre-embedding immunogold electron microscopy and to correlate light and electron microscopical immunogold labelling results.

Journal of Immunological Methods, epub ahead of print.

http://dx.doi.org/10.1016/j.jim.2017.02.003

StephanMaxeiner*, FujunLuo*, AlisonTan, FrankSchmitz, Thomas CSüdhof§ (2016)

How to make a synaptic ribbon: RIBEYE deletion abolishes ribbons in retinal synapses and disrupts neurotransmitter release.

EMBO J. 2016 Feb 29. pii: e201592701. [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/2692901

Wahl S*, Magupalli VG*, Dembla M*, Katiyar R*, Schwarz K*, Köblitz L, Alpadi K, Krause E, Rettig J, Sung C-H., Goldberg AFX, Schmitz F (2016)

The Disease Protein Tulp1 Is Essential for Periactive Zone Endocytosis in Photoreceptor Ribbon Synapses

Journal of Neuroscience 36(8): 2473-2493; doi: 10.1523/JNEUROSCI.2275-15.2016

* equal contributions

http://www.jneurosci.org/content/36/8/2473.short

Leon Lagnado and Frank Schmitz (2015)

Ribbon synapses and visual processing in the retina

Annual Review of Vision Science 1, 235-262.

http://www.annualreviews.org/toc/vision/1/1

Katiyar R*, Weissgerber P*, Roth E*, Dörr J, Sothilingam V, Garcia Garrido M, Beck SC, Seeliger M, Beck A, Schmitz F§, Flockerzi V§ (2015)
Influence of the β2-subunit of L-type voltage-gated Cav channels on the structural and functional development of photoreceptor ribbon synapses

*,§ equal contributions
Invest Ophthalmol Vis Sci. 2015 Mar 12. pii: IOVS-15-16654. doi: 10.1167/iovs.15-16654.

http://www.ncbi.nlm.nih.gov/pubmed/25766584

Anjum R, Ajoubian H, Schmitz F (2014)

Differential synaptic distribution of the scaffold proteins Cask and Caskin1 in the bovine retina

Mol Cell Neurosci 62, 19-29.

http://www.ncbi.nlm.nih.gov/pubmed/25123431

Mayur Dembla, Silke Wahl, Rashmi Katiyar, and Frank Schmitz
ArfGAP3 is a component of the photoreceptor synaptic ribbon complex and forms a NAD(H)-regulated, redox-sensitive complex with RIBEYE that is important for endocytosis

The Journal of Neuroscience,April 9, 2014.34(15):5245-5260

http://www.jneurosci.org/content/34/15/5245.full.pdf+html

Silke Wahl, Rashmi Katiyar and Frank Schmitz.

Fairless R, Williams SK, Hoffmann DB, Stojic A, Hochmeister S, Schmitz F, Storch MK, Diem R.

Preclinical retinal neurodegeneration in a model of multiple sclerosis.

J Neurosci. 2012 Apr 18;32(16):5585-97.

http://www.ncbi.nlm.nih.gov/pubmed/22393316

Grabner CP, Gandini MA, Rehak R, Le Y, Zamponi GW, Schmitz F.

RIM1/2-mediated facilitation of Cav1.4 channel opening is required for Ca2+-stimulated release in mouse rod photoreceptors.
J Neurosci. 2015 Sep 23;35(38):13133-13147

 http://www.ncbi.nlm.nih.gov/pubmed/26400943

Schauer C, Tong T, Petitjean H, Blum T, Peron S, Mai O, Schmitz F, Boehm U, Leinders-Zufall T (2015)

Hypothalamic gonadotropin releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle.

J Neurophysiol Jun 10:jn.00357.2015. doi: 10.1152/jn.00357.2015.

http://www.ncbi.nlm.nih.gov/pubmed/26063780

Schmitz F. (2014)

Presynaptic [Ca2+] and GCAPs: aspects on the structure and function of photoreceptor ribbon synapses.
Front. Mol. Neurosci., 06 February 2014 Volume 7 - 2014

http://www.frontiersin.org/molecular_neuroscience/10.3389/fnmol.2014.00003/abstract

Silke Wahl, Rashmi Katiyar and Frank Schmitz.
A Local, Periactive Zone Endocytic Machinery at Photoreceptor Synapses in Close Vicinity to Synaptic Ribbons.

The Journal of Neuroscience,2013 June 19;33(25)10278-10300April 9, 2014.34(15):5245-5260

http://www.jneurosci.org/content/33/25/10278.full.pdf+html

Matti U, Pattu V, Halimani M, Schirra C, Krause E, Liu Y, Weins L, Fang Chang H, Guzman R, Olausson J,Freichel M, Schmitz F, Pasche M, Becherer U, Bruns D, Rettig J.

Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion.

Nat Commun. 2013 Feb 5;4:1439. doi: 10.1038/ncomms2467

http://www.nature.com/ncomms/journal/v4/n2/full/ncomms2467.html

Elena Alvarez-Baron1,*, Katrin Michel1,*,Tobias Mittelstaedt1, Thoralf Opitz2,3, Frank Schmitz5,Heinz Beck2,3, Dirk Dietrich4, Albert J. Becker1, and Susanne Schoch1

RIM3γ and RIM4γ Are Key Regulators of Neuronal Arborization.

J Neurosci. 2013 Jan 9;33(2):824-39

http://www.jneurosci.org/content/33/2/824.full

Schmitz F, Natarajan S, Venkatesan JK, Wahl S, Schwarz K, Grabner CP.

EF hand-mediated Ca and cGMP signaling in photoreceptor synaptic terminals.

Front Mol Neurosci., 2012;5:26. Epub 2012 Feb 29.

http://www.ncbi.nlm.nih.gov/pubmed?term=22514320[uid]

Schwarz K*, Natarajan S*, Kassas N, Vitale N, Schmitz F

The Synaptic Ribbon Is a Site of Phosphatidic Acid Generation in Ribbon Synapses.

J. Neurosci., 2011 Nov 2; 31(44): 15996-16011. * gleichberechtigte Erstautoren.

http://www.jneurosci.org/content/31/44/15996.full

Ritter LM, Khattree N, Tam B, Moritz OL, Schmitz F, Goldberg AF.

In Situ Visualization of Protein Interactions in Sensory Neurons: Glutamic Acid-Rich Proteins (GARPs) Play Differential Roles for Photoreceptor Outer Segment Scaffolding.

J. Neurosci., 2011 Aug 3;31(31):11231-43.

http://www.jneurosci.org/content/31/31/11231.long

Venkatesan J.K.*, Natarajan S.*, Schwarz K.*, Mayer S.I., Alpadi K., Magupalli V.G. Sung C.-H., Schmitz F. (2010) NAD(H)-dependent binding of the neuronal Ca2+-sensor protein GCAP2 to photoreceptor synaptic ribbons.

J. Neurosci., 2010 May 12;30(19):6559-76.* gleichberechtigte Erstautoren.

http://www.ncbi.nlm.nih.gov/pubmed/20463219

Schmitz F. (2009) The making of synaptic ribbons: how they are built and what they do.

The Neuroscientist 15, 611-624.

http://www.ncbi.nlm.nih.gov/pubmed/19700740

Sorg H., Krueger C., Schulz T., Menger M.D., Schmitz F., Vollmar B. (2009) Effects of erythropoietin in skin wound healing are dose related.

FASEB J. 23, 3049-3058.

http://www.ncbi.nlm.nih.gov/pubmed/19403513

Schmitz, F., Fernandez-Chacon, R. (2009) Cysteine-string proteins.

The New Encyclopedia of Neuroscience3, 285-292.

Alpadi, K., Magupalli, V.G., Käppel, S., Köblitz, L., Schwarz, K., Seigel, G.M., Sung, C.H., Schmitz, F. (2008) RIBEYE recruits Munc119, the mammalian ortholog of the Caenorhabditis elegans protein unc119 to synaptic ribbons of photoreceptor synapses.

J. Biol. Chem. 283, 26461-26467.

http://www.ncbi.nlm.nih.gov/pubmed/18664567

Magupalli, V.G., Schwarz, K., Alpadi, K., Natarajan, S., Seigel, G.M., Schmitz, F. (2008) Multiple RIBEYE - RIBEYE interactions create a dynamic scaffold for the formation of synaptic ribbons.

J. Neurosci. 28, 7954-7967 (2008).

http://www.ncbi.nlm.nih.gov/pubmed/18685021

Ekici, M., Schmitz, F., Hohl, M., Seigel, G.M., Thiel, G. (2008) Chromatin structure and expression of synapsin I and synaptophysin in retinal precursor cells.

Neurochem. Int. 53, 165-172.

http://www.ncbi.nlm.nih.gov/pubmed/18692536

Wei C., Möller C.C., Altintas M.M., Li J., Schwarz K., Zacchigna S., Xie L., Heuger A., Schmid H., Rastaldi M.P., Cowan P., Kretzler M., Parilla R., Bendayan M., Gupta V., Nikolic B., Kalluri R., Carmeliet P., Mundel P., Reiser J. (2008) Modification of kidney barrier function by the urokinase receptor.

Nature Medicine 14, 55-63.

http://www.ncbi.nlm.nih.gov/pubmed/18084301

Vennekens, R., Olausson, J., Meissner, M., Bloch, W., Mathar, I., Philipp, S.E., Schmitz, F., Weissgerber, P., Nilius, B., Flockerzi, V., Freichel, M. (2007) Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4.

Nature Immunol. 3, 312-320.

http://www.ncbi.nlm.nih.gov/pubmed/17293867

Schoch, S., Mittelstaedt., T., Kaeser, P., Padgett, D., Feldman, N., Chevalevre V., Castillo, P.E., Hammer, R.E., Han,W., Schmitz, F., Lin, W., Südhof, T.C. (2006) Redundant functions of RIM1alpha and RIM2alpha in Ca²⁺-triggered neurotransmitter release.

EMBO J. 25, 5852-5863.

http://www.ncbi.nlm.nih.gov/pubmed/17124501

Schmitz, F., Tabares, L., Khimich, D., Strenzke, N., de la Villa-Polo, P., Castellano-Munoz, M., Bulankina, A., Moser, T., Fernandez-Chacon, R.F., Südhof, T.C. (2006) CSPalpha deficiency causes massive and rapid photoreceptor degeneration.

Proc. Natl. Acad. Sci. USA 103, 2926-2931.

http://www.ncbi.nlm.nih.gov/pubmed/16477021

Tom Dieck, S., Schmitz, F., Brandstätter, J.H. (2005) CtBPs as synaptic proteins. In: G. Chinnadurai (Ed.) CtBP family proteins, Landes Bioscience,

New York, Springer Press, pp. 105-111.

Schlüter, O., Schmitz, F., Jahn, R., Südhof, T.C. (2004) A complete genetic analysis of neuronal Rab3 function.

J. Neurosci. 24, 6629-6637.

http://www.ncbi.nlm.nih.gov/pubmed/15269275

Fernandez-Chacon, R., Wölfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M., Rosenmund, C., Montesinos, M.L., Sanes, J.R., Schneggenburger, R., Südhof, T.C. (2004) The synaptic vesicle protein CSPalpha prevents presynaptic degeneration.

Neuron 42, 237-251.

http://www.ncbi.nlm.nih.gov/pubmed/15091340

von Kriegstein, K., Schmitz, F. (2003) Expression and assembly of synaptic membrane proteins in ribbon synapses of the developing mouse retina.

Cell Tiss. Res. 311, 159-173.

http://www.ncbi.nlm.nih.gov/pubmed/12596036

Schoch, S., Castillo, P., Jo, T., Mukhargee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R.C., Südhof, T.C. (2002) RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.

 Nature 415, 321-326.

http://www.ncbi.nlm.nih.gov/pubmed/11797009

Castillo P, Schoch S, Schmitz F, Südhof T.C., Malenka R.C. (2002) Rim1a is required for presynaptic long-term potentiation.

Nature 415, 327-330.

http://www.ncbi.nlm.nih.gov/pubmed/11797010

Schmitz F. (2001) Immunological heterogeneity of synaptic and extrasynaptic forms of nonerythroid alpha-spectrin in the rat retina. 

Neurosci. Lett. 313, 25-28.

http://www.ncbi.nlm.nih.gov/pubmed/11684331

Schmitz F. , Augustin, I., Brose, N. (2001) Absence of the synaptic vesicle priming protein Munc13-1 from tonically active ribbon synapses of the rat retina.

Brain Res. 895, 258-263.

http://www.ncbi.nlm.nih.gov/pubmed/11259787

Schmitz F,Königstorfer A, SüdhofT.C.  (2000) RIBEYE, a component of ribbon synapses: A protein?s journey through evolution provides insight into synaptic ribbon function. 

Neuron 28, 857-872.

http://www.ncbi.nlm.nih.gov/pubmed/11163272

Butz S, Fernandez-Chacon R, Schmitz F, Jahn R, Südhof T.C. (1999) Synaptotagmin III is concentrated in synapses but excluded from synaptic vesicles: a synaptic synaptotagmin  absent from synaptic vesicles.

J. Biol. Chem. 274, 18290-18296.

http://www.ncbi.nlm.nih.gov/pubmed/10373432

von Kriegstein K, Schmitz F, Link E, Südhof T.C. (1999) Distribution of synaptic vesicle proteins in the mammalian retina identifies obligatory and facultative components of synapses.

Europ. J. Neurosci. 11, 1335-1348.

http://www.ncbi.nlm.nih.gov/pubmed/10103129

Kraemer J, Schmitz F, Drenckhahn D (1999) Cytoplasmic dynein and dynactin as likely candidates for microtubule-dependent apical targeting of pancreatic zymogen granules.

Europ. J. Cell Biol. 78, 265-277.

http://www.ncbi.nlm.nih.gov/pubmed/10350215

Wang Y, Okamoto M, Schmitz F, Hofmann K, Südhof T.C. (1997) RIM is a putative Rab3 effector in regulating synaptic - vesicle fusion.

Nature 388, 593-598.

http://www.ncbi.nlm.nih.gov/pubmed/9252191

Schmitz F , Bechmann M , Drenckhahn D (1996) Purification of synaptic ribbons, structural components of the active zone complex of photoreceptor synapses.

J. Neurosci. 16, 7109-7116.

http://www.ncbi.nlm.nih.gov/pubmed/8929420