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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Physiology
Molecular
Microbiology
Molecular Biophysics
Office: (214) 648-8445
Fax: (214) 648-4771
Email: pbloun@mednet.swmed.edu
Mechanosensitive Channels in Bacteria
Whether it is to sense a touch, arterial pressure, or an osmotic
gradient across a cell membrane, essentially all living organisms require the ability to
detect mechanical force. Electrophysiological evidence has suggested that mechanosensitive
ion channels play a major role in many systems where mechanical force is detected. But,
despite their biological importance, determination of the most basic structural and
functional features of mechanosensitive channels has only recently become possible.
A gene called mscL, originally isolated from Escherichia coli ,
is the first gene shown to encode a mechanosensitive channel activity. This channel
directly responds to tension in the membrane; no other proteins are required. Because of
the power of microbial genetics and the availability of structural information (the closed
structure was solved to 3.5Å resolution), the study of the MscL protein remains, to date,
one of the most viable options for understanding the structural and functional
characteristics of a mechanosensitive channel.
A major goal of our laboratory is to define the physiological role
and molecular mechanisms of MscL and other mechanosensitive channels found in microbes.
When assayed by patch clamp, three mechanosensitive channel activities are observed in the
inner membrane of E. coli . Studies in other bacteria have demonstrated
mechanosensitive channel activity and/or MscL homologues across a vast range of the
bacterial kingdom including Gram positive organisms and cyanobacteria. These channels play
an important role in osmoregulation by serving as “emergency release valves”
that are triggered upon sudden and severe hypo-osmotic stress. Not only have our studies
indicated that bacterial mechanosensitive channels may be valid pharmacological targets
for antibacterial agents, but also our findings have given us a first glimpse of the
architecture and molecular mechanisms of a channel gated by membrane tension. To study
these bacterial mechanosensitive channels we employ a wide variety of approaches including
bacterial genetics, whole-cell physiology, molecular and biochemical techniques, and patch
clamp of either native bacterial membranes or membrane proteins reconstituted into
artificial liposomes.
Reviews:
Blount P, and PC Moe (1999) Bacterial mechanosensitive channels:
integrating physiology, structure and function. Trends in Microbiology 7:
420-424.
Blount P, SI Sukharev, PC Moe, B Martinac and C Kung (1999)
Mechanosensitive channels of bacteria. Methods Enzymol 294: 458-482.
Sukharev SI, P Blount, B Martinac and C Kung (1997) Mechanosensitive
channels of Escherichia coli : the MscL gene, protein and activities. Annu Rev
Physiol 59: 633-657
Primary Publications:
Ou X, P Blount, RJ Hoffman and C Kung (1998) One face of a
transmembrane helix is crucial in mechanosensitive channel gating. Proc Natl Acad Sci
USA 95:11471-11475
Blount P, SI Sukharev, PC Moe, MJ Schroeder, HR Guy, and C Kung (1996). Membrane
topology and multimeric structure of a mechanosensitive channel protein of Escherichia
coli . EMBO J 15:4798-4805
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Last updated: 17 Nov 2000
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