Compartment-specific phosphoinositide dynamics in a central neuron
Prof. Dr. Dominik Oliver
Institute for Physiology und
Philipps Universitity Marburg
phone: ++49 6421 2866444
fax: ++49 6421 2862306
Phosphoinositides (PIs) control many cellular processes including synaptic function and ion channel activity. We will use hippocampal pyramidal neurons as a model to investigate compartmentation of PI signaling. Changes in phosphatidylinositol(4,5)bisphosphate (PIP2) and phosphatidylinositol-(3,4,5)trisphosphate levels in response to a variety of physiological stimuli will be examined using FRET imaging. Particular attention will be paid to the highly compartmentalized dendritic compartments and postsynaptic spines. The dependence of ion channel activity and synaptic function on PIP2 will be probed with novel tools for spatiotemporally controlled depletion of PIP2.
Genetically encoded tools for the manipulation of PI concentrations in living cells. (A) Voltage-activated PIP2-phosphatase Ci-VSP. (B) Chemical recruitment of the PIP2-degrading phosphatase Inp54p to the plasma membrane. Addition of rapamycin induces dimerization of the FRB domain of mTOR and the cytosolic FKBP protein fused to Inp54p. Because FRB fusion to the lyn11 provides membrane anchoring via palmitoylation and myristoylation, rapamycin-triggered dimerization forces the previously cytosolic Inp54p to the membrane. (C) Strategy for light-triggered recruitment of Inp54p. PhyB binds the chromophore phycocyanobilin (PCB) to form a light-sensitive holoprotein, which undergoes reversible conformational changes triggered by red and infrared light. Only the red-light induced state allows for association of the PIF domain. Plasma membrane anchoring by a C-terminal CAAX motif results in recruitment of PIF or PIF fusion constructs to the membrane upon illumination with red light.
Sandra Hackelberg, PhD student
Michael Leitner, PhD student
Olga Ivanova, PhD student
Anja Feuer, PhD student
Gisela Fischer, lab technician
Dr. Christian R. Halaszovich, Postdoc
Dr. Daniela N. Schreiber, Postdoc
Publications since 2007
Halaszovich CR, Leitner MG, Le A,
Frezza L, Feuer A, Schreiber DN, Villalba-Galea CA, Oliver D (2012). A
human phospholipid phosphatase activated by a transmembrane control
module. J Lip Res doi: 10.1194/jlr.M026021
Leitner MG, Feuer A, Ebers O,
Schreiber DN, Halaszovich CR, Oliver D (2012). Restoration of ion
channel function in deafness-causing KCNQ4 mutants by synthetic channel
openers. Br J Pharmacol 165:2244-2259.
Schaechinger TJ, Gorbunov D,
Halaszovich CR, Moser T, Kugler S, Fakler B, Oliver D (2011). A
synthetic prestin reveals protein domains and molecular operation of
outer hair cell piezoelectricity. EMBO J
Lindner M., Leitner M.G., Halaszovich C.R., Hammond G.R., Oliver D. (2011). Probing the regulation of TASK potassium channels by PI(4,5)P2 with switchable phosphoinositide phosphatases. J Physiol 589:3149-3162
Lacroix J, Halaszovich CR, Schreiber DN, Leitner MG, Bezanilla F, Oliver D, Villalba-Galea CA (2011). Controlling the Activity of a Phosphatase and Tensin Homolog (PTEN) by Membrane Potential. J Biol Chem 286:17945-17953
Leitner M.G., Halaszovich C.R., Oliver D. (2011). Aminoglycosides inhibit KCNQ4 channels in cochlear outer hair cells via depletion of phosphatidylinositol(4,5)bisphosphate. Mol Pharmacol 79:51-60
Reisinger E., Meintrup D., Oliver D., Fakler B. (2010). Gene expression associated with the onset of hearing detected by differential display in rat organ of Corti. Eur J Hum Genet 18:1327-1332.
Halaszovich C.R., Schreiber D.N., Oliver D. (2009). Ci-VSP is a depolarization-activated phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase. J Biol Chem 284:2106-2113.
Schaechinger T.J., Oliver D. (2007). Nonmammalian orthologs of prestin (SLC26A5) are electrogenic divalent/chloride anion exchangers. Proc Natl Acad Sci USA 104:7693-7698.