The Laboratory of Michael J. Welsh
The Study of the Small Heat Shock Proteins within the Testes and Muscle
Tissue
Welcome
to our lab's web page. We study what are celled the small heat shock
proteins. Hsp27 and
alphaB-crystallin are the best studied of these proteins, but 8 additional
members of this protein family are known.
Very little is known about the function of most of these proteins. The proteins are called heat shock
proteins because cells usually increase synthesis of the proteins when cells are
heated slightly. When cells contain
more hsp27 or alphaB-crystallin, the cells are able to withstand what would
otherwise be a lethal high temperature.
In addition to heat stress, other stresses such as toxicants (e.g.
cadmium chloride), cytokines and growth factors induce the synthesis and/or
phosphorylation of hsp27, and when this ahppens the cells are more resistant to
the toxic stress. In muscle cells
as many as seven of the small heat shock proteins are synthesized
constitutively and several are found aligned with the thin filaments. The functions of these proteins in
muscle are not understood.
The manner
in which hsp27 and alphaB-crystallin protetct cells during stress and in normal
physiology is not fully understood.
Hsp27 and alphaB-crystallin have been proposed to function in
stabilizing actin filaments, although why stabilizing actin filaments would
protetct cells as also not understood.
Actin is one of the major components that makes up part of the
scaffolding of the cell cytoskeleton.
Actin also plays a role in specialized cell structures such as the tight
junctions between Sertoli cells.
These tight junctions act as a barrier to prevent the passage of certain
chemicals and nutrients between cells.
In addition, the small heat shock proteins may be playing a role as
molecular chaperones. This means
they might have the ability to either sequester degraded proteins or help fold
proteins into their correct three-dimensional state. The small heat shock proteins may also have other
functions. Experiments have
suggested that several of the small heat shock proteins may bind to and
regulate the function of other proteins.
Thus, these proteins may act as parts of signaling pathways in cells.
Our lab has several
interests involving hsp27. We are
interested in what other proteins may bind to hsp27 and what role hsp27 may
play in regulating the proteins to which it binds. Thus, we are studying the functions of hsp27-binding proteins
and how interaction of these proteins with hsp27 may affect the binding
proteins. We are also interested
in understanding why muscle cells express so many of the small heat shock
proteins and what the functions of these proteins are in muscle. We are interested in gaining a detailed
understanding of how hsp27 or other small heat shock proteins can protect cells
from toxic conditions, and in how these proteins may be involved in regulation
of cytoskeleton structure or function.
We are also interested in how toxicants affect cells in tissues and
organs that are particularly sensitive to toxicants, such as the testis and
kidney. Our studies are directly
relevant to understanding the effects of chronic exposure to industrial or
environmental toxicants, the function of muscle, the development and spread of
cancer, and signaling pathways in a variety of cell types.
Last updated Jan, 2003.