Flucher Bernhard E., Univ.-Prof. Dr.phil.
MCBO Coordinator/Speaker

University / Clinic: Innsbruck Medical University
Institute: Department of Physiology and Medical Physics
Research Area: Physiology, Cell Biology

Email: bernhard.e.flucher@i-med.ac.at
Web: physiologie.i-med.ac.at/flucher/

Research Topic:
Voltage-gated calcium channels control many important cell functions including muscle contraction, synaptic transmission in neurons, and gene regulation. Our research focuses on the molecular mechanisms that allow the members of this channel family to perform these diverse tasks. Signaling specificity is achieved in that calcium channels function in the context of complex molecular machines, in which specific channel isoforms interact with a specific set of upstream regulators and downstream effectors. детское постельное белье Киев

The excitation-contraction apparatus in muscle and synapses in the brain are important examples of such calcium channel signaling machines. We study the molecular organization of calcium channels in specific subcellular compartments and the molecular basis of their distinct biophysical properties with a wide range of modern cell biological and physiological techniques in cultures of muscle and nerve cells from normal and mutant mice. детская постель киев

To understand the molecular mechanisms of how muscles contract and how nerve cells process information are principal goals of current cell biology and has important implications for understanding neurological diseases.

  Structural determinants of specific voltage-sensitivities of L-type calcium channels
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Role of calcium channels in AChR patterning and neuromuscular junction formation
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Selected publications:
  Mastrolia V, Flucher S, Obermair G, Drach M, Hofer H, Renström E, Schwartz A, Striessnig J, Flucher B, Tuluc P
Loss of α2δ-1 Calcium Channel Subunit Function Increases the Susceptibility for Diabetes
Diabetes. 2017 Jan 23. pii: db151349. doi: 10.2337/db16-0336. [Epub ahead of print]

  Findeisen F, Campiglio M, Jo H, Abderemane-Ali F, Rumpf C, Pope L, Rossen N, Flucher B, DeGrado W, Minor DL Jr.
Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.
ACS Chem Neurosci. 2017 Mar 17. doi: 10.1021/acschemneuro.6b00454. [Epub ahead of print]

  Campiglio M, Flucher B
STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads
Sci Rep. 2017 Jan 23;7:41003. doi: 10.1038/srep41003.

  Campiglio M, Flucher B
STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads
Sci Rep. 2017 Jan 23;7:41003. doi: 10.1038/srep41003.

  Benedetti B, Benedetti A, Flucher B
Loss of the calcium channel β4 subunit impairs parallel fibre volley and Purkinje cell firing in cerebellum of adult ataxic mice
Eur J Neurosci. 2016 Jun;43(11):1486-98. doi: 10.1111/ejn.13241. Epub 2016 Apr 18

  Tuluc P, Benedetti B, Costé de Bagneaux P, Grabner M, Flucher B
Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.
J Gen Physiol. 2016 Jun;147(6):437-49.

  Rzhepetskyy Y, Lazniewska J, Proft J, Campiglio M, Flucher B, Weiss N
A Cav3.2/Stac1 molecular complex controls T-type channel expression at the plasma membrane
Channels (Austin). 2016 Sep 2;10(5):346-354. Epub 2016 May 5

  Stanika R, Campiglio M, Pinggera A, Lee A, Striessnig J, Flucher B, Obermair G
Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology
Sci Rep. 2016 Oct 6;6:34528. doi: 10.1038/srep34528

  Flucher B, Tuluc P
How and why are calcium currents curtailed in the skeletal muscle voltage-gated calcium channels?
J Physiol. 2016 Nov 29. doi: 10.1113/JP273423. [Epub ahead of print]

  Benedetti B, Tuluc P, Mastrolia V, Dlaska C, Flucher B
Physiological and pharmacological modulation of the embryonic skeletal muscle calcium channel splice variant CaV1.1e.
Biophys J. 2015 Mar 10;108(5):1072-80.

  Kaur G, Pinggera A, Ortner N, Lieb A, Sinnegger-Brauns M, Yarov-Yarovoy V, Obermair G, Flucher B, Striessnig J
A Polybasic Plasma Membrane Binding Motif in the I-II Linker Stabilizes Voltage-Gated Cav1.2 Calcium Channel Function.
J Biol Chem. 2015 Aug 21;290(34):21086-100.

  Etemad Ahari S, Campiglio M, Obermair G, Flucher B
The juvenile myoclonic epilepsy mutant of the calcium channel β 4 subunit displays normal nuclear targeting in nerve and muscle cells.
Channels (Austin). 2014 May 29;8(4).

  Etemad Ahari S, Obermair G, Bindreither D, Benedetti A, Stanika R, Di Biase V, Burtscher V, Koschak A, Kofler R, Geley S, Wille A, Lusser A, Flockerzi V, Flucher B
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
J Neurosci. 2014 Jan 22;34(4):1446-61

  Campiglio M, Biase V, Tuluc P, Flucher B
Stable incorporation vs. dynamic exchange of β subunits in a native calcium channel complex.
J Cell Sci.126(Pt 9):2092-101. Epub 2013 Feb 27.

  Di Biase V, Tuluc P, Campiglio M, Obermair G, Heine M, Flucher B
Surface traffic of dendritic CaV1.2 calcium channels in hippocampal neurons.
J Neurosci. 2011 Sep 21;31(38):13682-94

  Tuluc P, Flucher B
Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants.
J Muscle Res Cell Motil. 2011 Dec;32(4-5):249-56. Epub 2011 Nov 5.

  Flucher B, Tuluc P
A new L-type calcium channel isoform required for normal patterning of the developing neuromuscular junction.
Channels (Austin). 2011 Nov-Dec;5(6):518-24. Epub 2011 Nov 1.

  Obermair G, Schlick B, Di Biase V, Subramanyam P, Gebhart M, Baumgartner S, Flucher B
Reciprocal interactions regulate targeting of calcium channel beta subunits and membrane expression of alpha1 subunit in cultured hippocampal neurons.
J. Biol. Chem., 285:5776-5791.

  Pirone A, Schredelseker J, Tuluc P, Gravino E, Fortunato G, Flucher B, Carsana A, Salvatore F, Grabner M
Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavα1S-subunit.
Am J Physiol Cell Physiol 299(6):C1345-54

  Tuluc P, Molenda N, Schlick B, Obermair G, Flucher B, Jurkat-Rott K
A CaV1.1 channel splice variant with high conductance and voltage-sensitivity alters EC-coupling in developing skeletal muscle
Biophys. J., 96:35-44.

  Subramanyam P, Obermair G, Baumgartner S, Gebhart M, Striessnig J, Kaufmann W, Geley S, Flucher B
Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells
Channels 5:343-55.

  Obermair G, Tuluc P, Flucher B
Auxiliary Ca2+ channel subunits: Lessons learned from muscle
Curr. Opin. Pharmacol., March 6

  Di Biase V, Obermair G, Szabo Z, Altier C, Sanguesa J, Bourenet E., Flucher B
Stable membrane expression of postsynaptic CaV1.2 calcium channel clusters is independent of interactions with AKAP79/150 and PDZ proteins
J. Neurosci., 28:13845-13855.

  Tuluc P, Kern G, Obermair G, Kugler G, Flucher B
Depletion of the a2d-1 subunit from L-type Ca2+ channel alters cardiac action potential duration and myoplasmic Ca2+ transients.
Proc. Natl. Acad. Sci. USA, 104:11091-11096

  Szabo Z, Obermair G, Cooper C, Zamponi G, Flucher B
Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons.
Eur. J. Neurosci. 24:709-718

  Flucher B, Obermair GJ, Tuluc P, Schredelseker J, Kern G, Grabner M
The role of auxiliary dihydropyridine receptor subunits in muscle.
J Muscle Res Cell Motil. 2005;26(1):1-6. Epub 2005 Oct 14.

  Obermair G, Kugler G, Baumgartner S, Tuluc P, Grabner M, Flucher B
The Ca2+ channel alpha2delta-1 subunit determines Ca2+ current kinetics in skeletal muscle but not targeting of alpha1S or excitation-contraction coupling.
J Biol Chem. 2005 Jan 21;280(3):2229-37. Epub 2004 Nov 9.

  Schredelseker J, Di Biase V, Obermair G, Felder E, Flucher B, Franzini-Armstrong C, Grabner M
The β1a subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle.
Proc Natl Acad Sci U S A, 102(47): 17219-24

  Obermair G, Szabo Z, Bourinet E, Flucher B
Differential targeting of the L-type Ca channel alpha (Ca1.2) to synaptic and extrasynaptic compartments in hippocampal neurons
Eur. J. Neurosci. 19, 2109-22

  Kugler G, Weiss R, Flucher B, Grabner M
Structural requirements of the dihydropyridine receptor alpha1S II-III loop for skeletal-type excitation-contraction coupling.
J. Biol. Chem., 279: 4721-4728

  Flucher B, Weiss R, Grabner M
Cooperation of two-domain Ca2+ channel fragments in triad targeting and restoration of excitation-contraction coupling in skeletal muscle.
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10167-72

  Wilkens C, Kasielke B, Flucher B, Beam K, Grabner M
Excitation-contraction coupling is unaffected by drastic alteration of the sequence surrounding residues L720-L764 of the alpha1S II-III loop.
Proc. Natl. Acad. Sci. USA, 98, 5892-5897

  Flucher B, Kasielke N, Grabner M
The triad targeting signal of the skeletal muscle calcium channel is localized in the C-terminus of the alpha1S subunit
J. Cell Biol., 151, 467-477