Abstract
Cholesterol, a major component of the plasma membrane, determines the physical properties of biological membranes and plays a critical role in the assembly of membrane microdomains. Enrichment or deprivation of membrane cholesterol affects the activities of many signaling molecules at the plasma membrane. Cell detachment changes the structure of the plasma membrane and influences the localizations of lipids, including cholesterol. Recent studies showed that cell detachment changes the activities of a variety of signaling molecules. We previously reported that the localization and the function of the Src-family kinase Lyn are critically regulated by its membrane anchorage through lipid modifications. More recently, we found that the localization and the activity of Lyn were changed upon cell detachment, although the manners of which vary between cell types. In this review, we highlight the changes in the localization of Lyn and a role of cholesterol in the regulation of Lyn’s activation following cell detachment.
Highlights
Cholesterol is a precursor for bile acid, steroid hormones, and vitamin D, and is a major component of cellular membranes [1]
Cholesterol is heterogeneously distributed between membranes and forms cholesterol-rich membrane raft domains, and may recruit particular molecules—such as GM1 and caveolin—and interfere with signal transduction at cellular membranes
Loss of cell–scaffold interactions translocates cholesterol and some lipid raft-related molecules from the plasma membrane to endomembranes; Src-family kinases, which can be distributed to both lipid rafts and non-raft membranes, are primarily localized to either endomembranes or the plasma membrane depending on cell lines in suspension culture
Summary
Cholesterol is a precursor for bile acid, steroid hormones, and vitamin D, and is a major component of cellular membranes [1]. The N-terminal Src homology (SH) 4 domain of Src-family kinases has a glycine residue that undergoes a post-translational modification with myristic acid, and some have one or two cysteine residues that can be modified with palmitic acid [10] These lipid modifications serve to anchor the Src-family kinases onto cellular membranes and affect their trafficking and localizations [11]. Activation of Src-family kinases following cell adhesion is involved in many downstream signaling pathways, from stabilization of adherens junctions in epithelial cells to rolling and spreading of leukocytes on endothelial cells [5,18]. Cell detachment can change the localizations of many molecules associated with the plasma membrane, including cholesterol and Src-family kinases. We will focus on the regulation of the activities of Src-family kinases following cell detachment, based on our recent results that show a strong relationship between the distribution of membrane cholesterol and the localizations of Src-family kinases
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