Biomedical Summer Undergraduate Research Experience Program
(B-SURE)
The University of Texas Health Science Center at San Antonio (UTHSCSA)
NICHOLSON,
Bruce J. (Biochemistry): Our laboratory is interested
in defining the structure and properties of the unique class of membrane
channels called gap junctions that allow the direct passage of ions, small
metabolites and secondary messengers between cells. The proteins that comprise
these channels, a family called connexins in the vertebrates , are diverse
in nature, with multiple members of the family being expressed in most
cells and tissues. It has become increasingly evident that this diversity
in connexin composition imparts differential regulatory and permeability
properties to these intercellular channels. Understanding the structural
basis underlying the different properties of connexins will be an essential
step in fully appreciating the specialized role that these structures play
in different tissues. Evidence that structural diversity has physiological
consequences is provided by the linkage of five very distinct human diseases
to defects in different connexin genes. Specifically, deafness is linked
to Cx26 and Cx31 mutations, a form of skin keratinopathy is linked to distinct
defects in Cx31, peripheral neuronal degeneration in Charcot Marie Tooth's
disease is linked to a plethora of Cx32 defects and catarracts are linked
to Cx50 defects. Similarly, knock-outs of different connexins in mice
have produced highly variable problems ranging from embryonic death (Cx26),
to increased susceptibility to tumors (Cx32 ) or cardiac arrhythmias (Cx40),
female sterility (Cx37 ) and eye catarracts (Cx46 and 50).
Bruce J. Nicholson's
Web Page.
Signaling pathways interacting with gap junctions.