Carol J. Deutsch, Ph.D.

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Professor of Physiology
Department: Physiology
Graduate Group Affiliations

Contact information
D200 Richards Building
3700 Hamilton Walk
Philadelphia, PA 19104-6085
Office: (215) 898-8014
Fax: (215) 573-5851
Education:
B.A. (Chemistry)
Brandeis University, Waltham, MA, 1966.
M. Phil (Organic Chem.)
Yale University, New Haven, CT, 1969.
Ph.D. (Phys. Chem.)
Yale University, New Haven, CT, 1972.
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Description of Research Expertise

Research Interests
Function and assembly of voltage-gated potassium channels.

Key words: voltage-gated K+ channels, C-type inactivation, gating kinetics, protein-protein interactions, oligomerization, channel assembly, biogenesis, ion channels, human T-lymphocytes.

Description of Research
The focus of my laboratory is molecular mechanisms underlying the assembly and function of voltage-gated potassium channels (Kv), with particular emphasis on Shaker channels and on Kv1.3, a channel in human T-lymphocytes. Kv channels have diverse and critical roles in both excitable and non-excitable cells. We use a range of approaches including biochemical, molecular biological, and electrophysiological techniques. The current projects are in two major areas: mechanisms of slow inactivation in Shaker K+ channels and biogenesis of Kv1.3.

Potassium channel activity in a cell depends on an ensemble of channel properties including permeation and gating. Permeant ions themselves modulate these properties, thereby suggesting a potential means of autoregulation of channel activity, which could be important for homeostatic electrical activity. Our long term goal is to understand the autoregulatory mechanisms by which permeant ions modulate and synergize pore properties, gating (specifically slow inactivation), and movement of the voltage sensor. Two main aims are pursued in the laboratory. The first aim investigates the mechanisms of permeant ion modulation of gating and permeation in potassium channels. Several hypotheses are considered by exploiting a series of Shaker mutants having different kinetics of slow inactivation. The second aim investigates whether ions in the selectivity filter modulate the movement of voltage sensors.

The second major area of investigation is devoted to elucidating the stepwise mechanisms by which a Kv channel acquires its secondary, tertiary, and quaternary structures. We are identifying key folding and oligomerization interactions in the N-terminal T1 domain and the pore region of Kv1.3 during biogenesis. In addition, we assess when, and in which compartment, secondary Kv conformations are achieved.

Rotation Projects

1. Examination of the hypothesis that ions in the selectivity filter of Kv Shaker modulate the movement of the voltage sensor, as manifest in the voltage dependence, kinetics, and magnitudes of gating currents. These studies will test whether P-type and C-type inactivation are coupled via a common cation-dependent mechanism.

2. Determine whether the pathology of long QT syndrome-associated mutants in the N-terminal PAS domain of a cardiac human K channel (HERG) is due to folding errors.

3. Determine pore region architecture of Kv1.3 during biogenesis. We hypothesize that some of the tertiary structure of the pore is formed in the ribosome/translocon/Kv peptide complex. We use a folding assay to determine when and how pore architecture is established in the Kv nascent monomer and tetramer.

Lab personnel:
Evan Ray, MD/PhD Thesis Student
Andrey Kosolapov, Postdoctoral Fellow
Jianli Lu, Research Specialist
J.Michael Robinson, Research Specialist
LiWei Tu, Senior Research Investigator
Jing Wang, Part-time Technician
Lily Wong, Part-time Dishwasher

Selected Publications

Deutsch, C.: The Birth of a Channel. Neuron 2003 Notes: Currently in press.

Kosolapov, A. and Deutsch, C.: Folding of the Voltage-gated K+ Channel T1 Recognition Domain. J. Biol. Chem. 278: 4305-13, 2003.

Deutsch, C.: Potassium channel ontology. Ann. Rev Physiol. 64: 19-46, 2002.

Deutsch, C.: Potassium channel ontogeny. Ann. Rev. Physiol. 64: 19-46, 2002.

Lu, J., Robinson, J.M., Edwards, D. and Deutsch, C: T1-T1 Interactions occur in the Endoplasmic Reticulum while nascent Kv peptides are still attached to ribosomes. Biochem. 40: 10934-10946, 2001.

Lu, J. and Deutsch, C.: Pegylation: A method for assessing topological accessibilities in Kv1.3. Biochem. 40: 13288-301, 2001.

Tu L., Wang J., Helm A., Skach WR., Deutsch C.: Transmembrane biogenesis of Kv1.3. Biochemistry 39(4): 824-36, Feb 1 2000.

Tu L., Deutsch C.: Evidence for dimerization of dimers in K+ channel assembly. Biophysical Journal 76(4): 2004-17, Apr 1999.

Sheng Z., Deutsch C.: Assembly of ion channels. Methods in Enzymology 293: 17-32, 1998.

Deutsch, C: The courtship and marriage of K+ channel subunits. in Biol. Skr. Dan. Vid. Selsk. 49: 107-113, 1998 Notes: (Proceedings of The Royal Danish Academy).

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Last updated: 03/18/2013
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