Cell Biology and Physiology
Molecular Biology
Developmental Biology
Protein Biochemistry
Structure and Ultrastructure

Gill, Donald L., Ph.D.
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.

Patterson, R.L., van Rossum, D.B., and Gill, D.L. (1999) "Store-operated Ca2+ entry: evidence for a secretion-like coupling process" Cell 98, 487-489.

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Interdisciplinary Training Program
in Muscle Biology
University of Maryland Graduate School, Baltimore
University of Maryland, Baltimore (UMB)
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