REGULATION OF ENDOPLASMIC-RETICULUM CA-ATPASE BY GLYCOLYSIS IN EUKARYOTIC CELLS

This paper reviews work by our and other laboratories that explores th e coupling between glycolysis and endoplasmic reticulum (ER)-Ca-ATPase s in regulating Ca2+ homeostasis in several cell types. Changes in int racellular Ca2+ ([Ca2+](in)) link interaction between hormones and cel l surface receptors with the initiation of specific cellular functions . Thus, changes in [Ca2+](in) mediate signal transduction mechanisms t hat modulate many physiological functions including cell growth, muscl e cell contractility, and exocytosis in secretory cells, In most eukar yotic cells, total cellular Ca2+ is in the millimolar range, yet only a fraction (i.e., nanomolar) is free in the cytosal. Cells use both ac tive and 'passive' mechanisms to maintain [Ca2+](in) within a narrow r ange. Active mechanisms include plasma membrane and endoplasmic/sarcop lasmic reticulum (ER/SR)-Ca-ATPases, Ca2+ channels (inositol tris-phos phate- and voltage-sensitive), and Na+/Ca2+ exchangers, 'Passive' mech anisms include Ca2+-binding proteins (e.g., calsequestrin, calmodulin, calreticulin). The relative contribution of active and 'passive' mech anisms to [Ca2+](in) homeostasis in a given cell is not known. Ca2+ mi ght move among several intracellular compartments, including the ER/SR , mitochondria, nucleus, Golgi apparatus, endosomes and lysosomes. The ubiquitous distribution of ER-Ca-ATPases in these intracellular organ elles suggests a major role of this pump in Ca2+ homeostasis, but the importance of intracellular compartments to [Ca2+](in) homeostasis is not well understood. Glucose has been suggested to have a role in regu lating some of these ion transport processes, Thus, the increased cell metabolism that follows glucose stimulation is associated with altere d [Ca2+](in) homeostasis. The precise mechanisms by which glucose or i ts metabolites modulate [Ca2+](in) homeostasis are unknown but might i nvolve regulation of ER-Ca-ATPases.