Vytautas K. Verselis

Professor
Structure-function studies of gap junction channels; voltage gating, and permeation.

Kennedy Center
Room 710
(718) 430-3680

Connexin Channel Stucture Function

The connexins comprise a family of membrane proteins that form channels that provide an important pathway for intercellular signaling in many tissues. Using a combination of molecular genetic, biophysical and imaging approaches, we study various aspects of connexin channel structure-function relationships. Ongoing projects include identification of pore-lining domains using substituted cysteine accessibility, examination of mechanisms of permeation through characterization and modeling of single channels and localization of gating structures by state-dependent accessibility of thiol-reactive agents and physical detection of movement associated with gating by attachment of conformation-sensitive probes. More recently, we have begun to examine interactions specifically between connexins expressed in neurons and glia. Studies include examination of transmission of the biological signaling molecules using Ca2+ imaging combined with the use of intercellular biosensors. Simplified systems using transfected cells examine modulatory effects of cyclic nucleotides and possible action through phosphorylation. Collaborative projects include studies of mechanisms of connexin channel formation using high-resolution fluorescence imaging of tagged connexins and analysis of novel splice variants of K+ channels from the Slo gene and their role in diabetes-related changes in cellular excitability.

 

Selected Publications

Bukauskas F.F. and Verselis V.K. (2004). Gap Junction Channel Gating. Biochim Biophys Acta 1662:42-60.

Kronengold J., Trexler E.B., Bukauskas F.F., Bargiello TA and Verselis V.K. (2003). Pore-lining residues identified by SCAM studies in Cx46 hemichannels. Cell Comm Adhes, 10:193-199.

Kronengold, J., Trexler, E.B., Bukauskas, F.F., Bargiello, T.A. and Verselis, V.K. (2003). Single-channel SCAM identifies pore-lining residues in the first extracellular loop and first transmembrane domains of Cx46 hemichannels. J Gen Physiol, 122:389-405.

Verselis, V.K. and Bukauskas, F.F. (2002). Connexin-GFPs shed light on regulation of cell-cell communication by gap junctions. Curr Drug Targets, 3(6):483-99.

Bukauskas, F.F., Bukauskas, A., Verselis, V.K. and Bennett, M.V.L. (2002). Coupling asymmetry of heterotypic connexin45/connexin 43-EGFP gap junctions: Properties of fast and slow gating mechanisms. Proc Nat Acad Sci (USA), 99:7113-7118.

Bukauskas, F.F., Jordan, K., Bukauskiene, A., Bennett, M.V.L., Lampe, P.D., Laird, D.W. and Verselis, V.K. (2000). Clustering of connexin 43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. Proc Nat Acad Sci (USA), 97:2556-2561.

Trexler, E.B., Bukauskas, F.F., Kronengold, J., Bargiello, T.A. and Verselis, V.K. (2000). The first extracellular loop domain is a major determinant of charge selectivity in connexin46 channels. Biophys J 79:3036-3051.

Trexler, E.B., Bennett, M.V.L., Bargiello, T.A. and Verselis, V.K. (1996). Voltage gating and permeation in a gap junction hemichannel. Proc Nat Acad Sci 93:5836-5841.

Verselis, V.K., Ginter, C.S. and Bargiello, T.A. (1994). Opposite voltage gating polarities of two losely related connexins. Nature 368:348-351.