Membrane lipid rafts, master regulators of hematopoietic stem cell retention in bone marrow and their trafficking

• Published in: Leukemia Vol. 29; no. 7; pp. 1452 - 1457
• Main Authors: Ratajczak, M Z, Adamiak, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2015; Nature Publishing Group
• Subjects: 631/136/532/1542; 631/532/1542; Animals; Bone marrow; Bone Marrow - physiology; c-Kit protein; Cancer Research; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell Movement - physiology; Cell regulation; Chemokines; Critical Care Medicine; CXCR4 protein; Genetic aspects; Glycoproteins; Glycosphingolipids; Hematology; Hematopoietic Stem Cell Mobilization; Hematopoietic stem cells; Homing; Humans; Integrity; Intensive; Internal Medicine; Lipid rafts; Lipids; Medicine; Medicine & Public Health; Membrane Lipids; Membrane Microdomains; Membranes; Oncology; Outer membranes; Paroxysmal nocturnal hemoglobinuria; Progenitor cells; Properties; Rac1 protein; Rafts; Receptors; Regulators; Retention; review; SDF-1 protein; Signal Transduction; Stem cell factor; Stem cells; Vascular cell adhesion molecule 1; VLA-4 antigen
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2015.66

Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein microdomains, known as lipid rafts, which float freely in the membrane bilayer. These structures have an important role in assembling signaling molecules (e.g., Rac-1, RhoH and Lyn) together with surface receptors, such as the CXCR4 receptor for α-chemokine stromal-derived factor-1, the α4β1-integrin receptor (VLA-4) for vascular cell adhesion molecule-1 and the c-kit receptor for stem cell factor, which together regulate several aspects of hematopoietic stem/progenitor cell (HSPC) biology. Here, we discuss the role of lipid raft integrity in the retention and quiescence of normal HSPCs in bone marrow niches as well as in regulating HSPC mobilization and homing. We will also discuss the pathological consequences of the defect in lipid raft integrity seen in paroxysmal nocturnal hemoglobinuria and the emerging evidence for the involvement of lipid rafts in hematological malignancies.