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Paul L. Sorgen Paul L. Sorgen

Associate Professor, Biochemistry and Molecular Biology
Ph.D., University of Florida, 1999
Phone: (402) 559-7557 (Office)
(402) 559-7566 (Lab)
Fax: (402) 559-6650

 Email: psorgen@unmc.edu

 

Connexins are integral membrane proteins that oligomerize to form intercellular gap junction channels. These channels provide diffusional intercellular exchange of ions and small molecules, allowing individual cell events to synchronize into the functional response of an entire organ. Gap junctions mediate vitally important processes such as impulse propagation, regulation of cell growth, and organ development. Moreover, mutations in a gap junction protein are linked to various inherited diseases, including nervous system disorders, deafness, cataracts, heart defects, and skin diseases. While there is considerable information regarding key interactions of connexins in the regulation of gap junction channels, the precise mechanisms that lead to channel closure have not been defined, nor have the critical accessory proteins involved been fully characterized. This information is pivotal if intercellular communication in normal and diseased states is to be fully understood. Our laboratory is focused on using molecular, biological, and biochemical techniques to help define the mechanism of gap junction channel closure by pH and phosphorylation.
 

Model of a Gap Junction Channel Model of a Connexin with Cellular Partners

Model of a Gap Junction Channel. Gap junctions are formed by the apposition of connexons from adjacent cells, where each connexon is formed by six connexin proteins The channel location has been indicated by the yellow circle.

Model of a Connexin with Cellular Partners. Connexins are tetraspan transmembrane domain proteins with intracellular N- and C-termini. There are 21 different connexin genes in the human genome. The abbreviations are as follows: NT, N-terminus; CL, cytoplasmic loop; CT, C-terminus; E1 and E2, extracellular loops 1 and 2; 1-4, transmembrane segments 1-4.

 

Research Opportunities in my Lab 

Graduate Students

Post-Doctoral Positions, full time

Medical students, summer research

Undergraduate students, summer research

 

 

SORGEN LAB
Sorgen Lab 2009

Rosslyn Grosely, 4th year Graduate Student; Paul Sorgen, Associate Professor; 

Gaelle Spagnol, Postdoctoral Research Associate; Jennifer Kopanic, 3rd year

Graduate Student; Sarah Brownell, Research Technologist; Kelly Virgil, 4th year Graduate Student.

 

 

MOST RECENT PUBLICATIONS:

  1. Kieken, F., Jovic, M., Naslavsky, N., Caplan, S., and Sorgen, P. (2009) Structural mechanisms for NPF, DPF and GPF interaction with the C-terminal EH-domain of EHD1. Protein Science, in press. 
  2. Kieken, F., Mutsaers, N., Dolmatova, E., Virgil, K., Wit, A.L., Kellezi, A., Hirst-Jensen, B.J., Duffy, H.S., and Sorgen, P.L. (2009) Structural and molecular mechanisms of gap junction remodeling in epicardial border zone myocyctes following myocardial infarction.  Circ Res. 104(9):1103-12. Abstract
  3. Jovic, M., Kieken, F., Naslavsky, N., Sorgen P.L., and Caplan, S.  (2009) EHD1-associated tubules contain phosphatidylinositol-4-phosphate and phosphatidylinositol-(4,5)-bisphosphate and are required for efficient recycling.  Mol Biol Cell. 20(11):2731-43.  Abstract 
  4. Sorgen, P.L., and Delmar, M. (2008) Structure and organization of the cardiac gap junctions. In Cardiac Electrophysiology: From Cell to Bedside (Fifth Edition). Eds. Zipes, D.P. and Jalife, J. In press. 
  5. Bouvier, D., Kieken, F., Kellezi,A., and Sorgen, P.L. (2008) Structural Changes in the Carboxyl Terminus of the Gap Junction Protein Connexin40 caused by c-Src and Zonula Occludens-1. Cell Communication and Adhesion. 15:107-118.  Abstract 
  6. Kellezi, A. Grosely, R., Kieken, F., Borgstahl, G.E.O., and Sorgen, P.L. (2008) Purification and Reconstitution of the Connexin43 Carboxyl Terminus attached to the 4th Transmembrane Domain in Detergent Micelles. Protein Purification and Expression. 59:215-222.  Abstract
  7. Duffy, H.S., Kieken, F., Mutsaers, N. Ciaccio, E.J., Coromilas, J., Wit, A.L., and Sorgen, P.L. (2008)  Molecular Mechanisms of Connexin43 Lateralization in Ischemic Ventricular Myocytes after Coronary Artery Occlusion in the Canine Heart. Circulation. 116:67-68.
  8. Solan, J.L., Marquez-Rosado, L., Sorgen, P.L., Thornton, P.J., Gafken, P.R., and Lampe, P.D. (2007) Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents downregulation of PKC. J. Cell Biology. 179:301-1309. Abstract
  9. Kieken, F., Jovic, M., Naslavsky, N., Caplan, S.*, and Sorgen, P.L.* (2007) NMR structure note: EH domain of EHD1. J. Biomolecular NMR. 39:323-329. ±   Abstract
  10. Bouvier, D., Kieken, F., and Sorgen, P.L.# (2007). 1H, 13C, and 15N Backbone Resonance Assignments of the Carboxyl Terminal Domain of Connexin40. J. Biomolecular NMR Assignments. Epub ahead of print. 
  11. Lewandowski, R., Shibayama, J., Oxford, E.M., Joshi-Mukherjee, R., Coombs, W., Sorgen, P.L., Taffet, S.M., and Delmar, M. (2007). Chemical Gating of Connexin Channels. Connexins: A Guide. Eds. Harris, A.L. and Locke D. Springer, Secaucus, NJ.
  12. Naslavsky, N., Rahajeng, J., Chenavas, S., Sorgen, P.L.#, and Caplan, S.# (2007). EHD1 and Eps15 interact with phosphatidylinositols via their EH-domains. J. Biol. Chem. 282: 16612-16622.  Abstract
  13. Duffy, H.S., Iacobas, I., Hotchkiss, K., Hirst-Jensen, B., Bosco, A., Dandachi, N. Dermietzel, R., Sorgen, P.L., and Spray, D.C. (2007).  The gap junction protein Connexin32 interacts with the SH3/Hook domain of Discs Large homolog 1. J. Biol. Chem. 282:9789-9796. Abstract
  14. Hirst-Jensen, B.J., Sahoo, P., Kieken, F., Delmar, M., and Sorgen, P.L.# (2007).  Characterization of the pH-dependent interaction between the gap junction protein connexin43 carboxyl terminal and cytoplasmic loop domains. J. Biol. Chem. 282:5801-5813.  Abstract
  15. Shibayama, J., Gutiérrez, C., González, D., Kieken, F., Seki, A., Carrión, J.R., Sorgen, P.L., Taffet, S.M., Barrio, L.B., and Delmar, M. (2006). Effect of charge substitutions at residue his-142 on voltage gating of connexin43 channels. Biophys. J. 91:4054-4063.  Abstract
  16. Shibayama, J., Lewandowski, R., Kieken F., Coombs, W., Shah, S., Sorgen, P.L., Taffet, S.M., and Delmar, M. (2006). Identification of a Novel Peptide That Interferes With the Chemical Regulation of Connexin43. Circ Res. 98:1365-1372.  Abstract

FURTHER PUBLICATIONS:

  1. Sorgen, P.L. (2005). How to solve a protein structure by nuclear magnetic resonance - The Connexin43 carboxyl terminal domain. Practical Methods in Cardiovascular Research.  Eds. Dhein, S., Mohr, F.W, and Delmar.  M. Springer Berlin Heidelberg New York. 
  2. Sorgen, P.L.#, Duffy, H.S. Sahoo, P., Coombs W., Delmar M., and Spray, D.C. (2004). Structural changes in the carboxyl terminus of the gap junction protein Connexin43 indicates signaling between binding domains for c-Src and Zonula Occludens-1. J. Biol Chem. 279:54695-54701. 
  3. Sorgen, P.L.#, Duffy, H.S., S.M., Spray, D.C., and Delmar, M. (2004). pH-Dependent Dimerization of the Carboxyl Terminal Domain of Cx43.  Biophys. J. 87:574-581. 
  4. Delmar M., Coombs W., Sorgen P.L., Duffy H.S., and Taffet S.M. (2004). Structural bases for the regulation of Connexin43 channels. Cardiovasc Res. 62:268-275. 
  5. Delmar, M., Duffy, H.S., Sorgen, P.L, Taffet, S.M., and Spray, D.C. (2004).  Molecular organization and regulation of the cardiac gap junction channel Connexin43.  Cardiac Electrophysiology: From Cell to Bedside.  Eds. Zipes, D.P., and Jalife, J.  Saunders, Philadelphia, PA. 
  6. Krueger-Koplin, R.D., Sorgen, P.L., Krueger-Koplin, S.T., Cahill, S.M., and Girvin, M.E. (2004).  Optimal detergents and their use in structural mechanistic NMR studies of membrane proteins.  J. Biomol.  NMR 28:43-57. 
  7. Sorgen, P.L.*, Hu, Y.*, Guan, L., Kaback, R., and Girvin, M.E. (2002). Structure of the lactose permease determined from non-traditional constraints.   Proc. Natl. Acad. Sci. USA 99:14037-14040. 
  8. Duffy, H.S.*, Sorgen, P.L.*, Girvin, M.E., O'Donnell, P., Coombs, W., Tafft, S.M., Delmar, M., and Spray, D.C.  (2002). pH-dependent intramolecular binding and structure involving Cx43 cytoplasmic domains.  J. Biol. Chem. 277:36706-36714. 
  9. Sorgen, P.L., Duffy, H.S., Cahill, S.M., Coombs, W., Spray, D.C., Delmar, M., and Girvin, M.E.  (2002).  Letter to the Editor: Sequence-specific assignment of the carboxyl terminal domain of Connexin43.  J. Biomol. NMR 23:245-246. 
  10. Sorgen, P.L., Cahill, S.M., Krueger-Koplin, R.D., Krueger-Koplin, S.T., Schench, C.C., and Girvin, M.E.  (2002). Structure of the Rhodobacter sphaeroides light-harvesting 1 β subunit in detergent micelles.  Biochemistry 41:31-41.
  11.  Sorgen, P.L., Bubb, M.R., and Cain, B.D.  (1999). Lengthening the second stalk of F1F0 ATP synthase in Escherichia coli.  J. Biol. Chem. 274:36261-36266. 
  12. Sorgen, P.L., Caviston, T.L., Perry, R.C., and Cain, B.D.  (1998). Deletions in the second stalk of F1F0 ATP synthase in Escherichia coli.  J. Biol. Chem. 273:27873-27878. 
  13. Caviston, T.L., Ketchum, C.J., Sorgen, P.L., Nakamoto, R.K., and Cain, B.D.  (1998). Identification of an uncoupling mutation affecting the β subunit of F1F0 ATP snythase in Escherichia coli.  Febs. Lett. 429:201-206. 
  14. Sorgen, P.L., Bubb, M.R., McCormick, K.A., Edison, A.S., and Cain, B.D.  (1998). Formation of the β subunit dimmer is necessary for interaction with F1-ATPase.  Biochemistry 37:923-932.

*Co-first author 

#Corresponding author(s)

±Image from paper chosen for journal cover of J. Biomolecular NMR, 2008.

 

 

Grants and Contracts-current:

Mechanisms of Gap Junction Regulation

National Institutes of Health (RO1)

04/01/2006 - 03/31/2011

Principal Investigator: Paul Sorgen

 

Graduate Training in Structural Biology and Biophysics

Department of Education

08/15/2006-08/14/2009

Co-Principal Investigators: Paul Sorgen, Gloria Borgstahl, and Luis Marky

 

Nebraska Center for Structural Biology

Nebraska Research Initiative Project Grant

07/01/2004 – 06/30/2009

Principal Investigator: Gloria Borgstahl; Co-Investigators: Paul Sorgen, Joseph Barycki

 

Intercellular Communication and Impulse Propagation 

National Institutes of Health (PO1)

09/01/2006 - 08/31/2011

Principal Investigator: Jose Jalife; Sub-Contract: Paul Sorgen

 

EHD1-mediated Regulation of  β1 Integrin Function

Nebraska Health and Human System (LB506) Award

07/01/2008 - 06/30/2009

Principal Investigator: Paul Sorgen

 

Molecular characterization of the intercalated disc in models of arrhythmogenic right ventricular cardiomyopathy

National Institutes of Health (PO1)

09/01/2007 - 08/31/2012

Principal Investigator: Jose Jalife; Sub-Contract: Paul Sorgen

 

Thermo Scientific NanoDrop 1000 UV-Vis Spectrophotometer for Protein Analysis

Nebraska Bankers Association

07/01/2008 - 06/30/2009

Principal Investigator: Paul Sorgen