title: Leukocyte adhesion and polarization: Role of glycosylphosphatidylinositol-anchored proteins.
abstract: Leukocyte traffic out of the blood stream is crucial for an adequate immune response. Leukocyte extravasation is critically dependent on the binding of leukocyte integrins to their endothelial counterreceptors. This interaction enables the firm adhesion of leukocytes to the luminal side of the vascular wall and allows for leukocyte polarization, crawling and diapedesis. Leukocyte adhesion, polarization and migration requires the orchestrated regulation of integrin adhesion/de-adhesion dynamics and actin cytoskeleton rearrangements. Adhesion strength depends on conformational changes of integrin molecules (affinity) as well as the number of integrin molecules engaged at adhesion sites (valency). These two processes can be independently regulated and several molecules modulate either one or both processes. Cholesterol-rich membrane domains (lipid rafts) participate in integrin regulation and play an important role in leukocyte adhesion, polarization and motility. In particular, lipid raft-resident glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs) have been reported to regulate leukocyte adhesion, polarization and motility in both integrin-dependent and independent manners. Here, we present our recent discovery concerning the novel role of the GPI-AP prion protein (PrP) in the regulation of β1 integrin-mediated monocyte adhesion, migration and shape polarization in the context of existing literature on GPI-AP-dependent regulation of integrins.
authors.affiliation: a Deptartment of Molecular Cell Biology ; Sanquin Research and Landsteiner Laboratory; University of Amsterdam ; Amsterdam , Netherlands.
authors.forename: Dion D
authors.initials: DD
authors.lastname: Richardson
authors.affiliation: a Deptartment of Molecular Cell Biology ; Sanquin Research and Landsteiner Laboratory; University of Amsterdam ; Amsterdam , Netherlands.
authors.forename: Mar
authors.initials: M
authors.lastname: Fernandez-Borja
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D016764:Cell Polarity; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D016023:Integrins
keywords: ERM; GPI-anchored protein; diapedesis; integrin; leukocyte; lipid raft; migration; polarization; uropod