Session 7, Abstract 40

THE EFFECT OF GLUCOSE CONCENTRATION ON SOLUBLE CRIPTO LEVELS AND CELLULAR LOCALIZATION

Erika Duell*​1​ and Malachia Hoover​1​ (Jonathan Kelber​1​), California State University Northridge, Dept. of Biology, 18111 Nordhoff St., Northridge, CA 91330. 

Cripto is a cell surface, GPI-anchored glycoprotein known to regulate TGF and mitogenic signaling pathways, and it is a key regulator of stem cell function in development and cancer. Cripto signaling and function requires the expression and binding of the heat shock protein GRP78 (BiP). In this regard, Cripto functions in its GPI-anchored state as well as a GPI anchor-cleaved and soluble form. While GRP78 is known to be upregulated by low glucose-induced cellular stress, the role that glucose and GRP78 play on Cripto subcellular localization remains unclear. Here we demonstrate that soluble Cripto is significantly increased in concert with GRP78 upregulation following glucose deprivation of mammary epithelial cells. These and future studies investigating the underlying mechanisms of Cripto transport to the plasma membrane and GPI anchor cleavage are likely to uncover key regulatory pathways relevant in both the normal and disease physiology of Cripto.

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