Philadelphia University + Thomas Jefferson University

Levitan, Irwin

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Irwin Levitan, PhD

Contact Dr. Levitan

900 Walnut Street
JHN 4th floor
Philadelphia, PA 19107

(215) 503-5996
(215) 503-4358 fax

Research and Clinical Interests

My laboratory is interested in the long term regulation of neuronal excitability and synaptic transmission. We study the molecular mechanisms that nerve cells use to modulate the activity of individual ion channels, since these mechanisms must contribute to long term changes in neuronal function and ultimately in behavior.

The essence of our approach is a combination of biochemistry, molecular biology, genetics and electrophysiology, at the level of individual neurons, synapses and ion channels. We study the electrophysiological properties of native channels in neurons, and of cloned channels expressed in heterologous host cells, using patch recording techniques. In parallel we carry out biochemical measurements of channel proteins, making use of specific antibodies directed against channel epitopes. An important theme that we are pursuing vigorously is the idea that channels do not exist on their own in the plasma membrane, but rather are part of a regulatory complex that includes signaling proteins that are involved in the modulation of channel function. For example, we have isolated a novel protein named Slob, which binds to and modulates the Slowpoke calcium-dependent potassium channel in the fruit fly Drosophila. We are investigating the molecular details and physiological significance of the dynamic interactions of Slob and other signaling proteins with several different kinds of potassium channels. One way we do this is by using genetics to introduce mutant channels and their binding partners into flies to ask questions about the roles of ion channel regulatory complexes in neuronal physiology and behavior.

Publications

Most Recent Peer-Reviewed Publications

  1. Defects in synapse structure and function precede motor neuron degeneration in Drosophila models of FUS-related ALS
  2. Cell-specific fine-tuning of neuronal excitability by differential expression of modulator protein isoforms
  3. Slob, a slowpoke channel-binding protein, modulates synaptic transmission
  4. Identification of a Neural Circuit that Underlies the Effects of Octopamine on Sleep:Wake Behavior
  5. In vivo role of a potassium channel-binding protein in regulating neuronal excitability and behavior
  6. miXED Messages in Ion Channel Modulation
  7. In Vivo Roles of Ion Channel Regulatory Protein Complexes in Neuronal Physiology and Behavior
  8. Drosophila ortholog of succinyl-CoA synthetase β subunit: A novel modulator of Drosophila KCNQ channels
  9. Mechanisms of two modulatory actions of the channel-binding protein slob on the Drosophila slowpoke calcium-dependent potassium channel
  10. Signaling protein complexes associated with neuronal ion channels
  11. Expression and function of variants of Slob, Slowpoke channel binding protein, in Drosophila
  12. Expression of a calmodulin-binding KCNQ2 potassium channel fragment modulates neuronal M-current and membrane excitability
  13. A Drosophila KCNQ channel essential for early embryonic development
  14. MONaKA, a novel modulator of the plasma membrane Na,K-ATPase
  15. The amino terminus of slob, slowpoke channel binding protein, critically influences its modulation of the channel
  16. Syntaxin-1A binds to and modulates the Slo calcium-activated potassium channel via an interaction that excludes syntaxin binding to calcium channels
  17. The slowpoke channel binding protein Slob from Drosophila melanogaster exhibits regulatable protein kinase activity
  18. A Well-Stocked Pool
  19. An interaction domain in Slob necessary for its binding to the slowpoke calcium-dependent potassium channel
  20. Monomeric 14-3-3 protein is sufficient to modulate the activity of the Drosophila Slowpoke calcium-dependent potassium channel