Gill, Donald L., Ph.D., Professor
Department of Biochemistry and Molecular Biology
E-mail: dgill@umaryland.edu
Gill, Donald L., Ph.D., Professor
Department of Biochemistry and Molecular Biology
E-mail: dgill@umaryland.edu
Presently, we are looking at the mechanism of action of the
intracellular messenger inositol
1,4,5-triphosphate (InsP3) which directly activates Ca2+
release from ER and hence mediates the
Ca2+-signaling events related to receptor action. Recent
studies in this laboratory have revealed a
new Ca2+-translocation mechanism in ER which is controlled by a
highly sensitive and specific
guanine nucleotide regulatory mechanism. This mechanism appears
to release Ca2+ from the same
pool as InsP3 via a distinct mechanism. Current studies are
identifying the molecular components of
this Ca2+ translocation process and investigating the exciting
possibility that a protein related to a
new group of small (20 25 kDa) monomeric G proteins is
mediating the intercompartmental transfer
of Ca2+ within cells.
Recently, studies have also been initiated on the role of
sphingolipids in the control of in-
tracellular Ca2+. We have discovered that sphingosine
metabolites produced at the ER membrane
can induce profound movements of Ca2+ across the ER membrane,
resulting in emptying of the
InsP3-releasable Ca2+ pool. It appears that an enzyme, probably
sphingosine kinase, exists in the
ER membrane and converts free sphingosine into
sphingosine-1-phosphate, which is active in
releasing Ca2+. The possibility exists that sphingolipid
breakdown resulting in modification of both
protein kinase C activity and Ca2+ mobilization may represent a
signaling pathway as important as
and complementary with the phosphoionositide/Ca2+-signaling
pathway in cells.
The research involves study of these mechanisms in a variety
of cultured clonal neural and mus-
cle cell lines, as well as vesicular membrane fractions
isolated from excitable tissues. In addition to
investigating Ca2+ regulation within cells, parallel studies
continue on regulation of ion fluxes across
the plasma membrane. Thus, through a range of biochemical and
cellular approaches, we are
addressing some fundamental questions of cellular signal
transduction in mammalian cells.
Graber, M.N., Alfonso, A., and Gill, D.L., "Ca2+ pools and cell
growth: Arachidonic acid induces
recovery of cells growth-arrested by Ca2+ pool depletion", JBC,
271:883-888, 1996.