title: The erythroid niche: molecular processes occurring within erythroblastic islands.
abstract: Erythroblasts terminally differentiate within specialized niches composed of erythroblast islands nesting in extracellular matrix proteins. A number of adhesion molecules active in erythroid island attachments have been identified. We have recently observed a receptor/counter receptor interaction that appears to maintain island integrity: erythroid ICAM-4 interacting with macrophage alphaV integrin. When ICAM-4/alphaV binding is blocked, a 70% decrease in islands is observed. Moreover, erythroblastic islands are markedly decreased in ICAM-4 null mice. Using erythropoietin to examine whether ICAM-4/alphaV binding plays a role in stress erythropoiesis, we found that the reticulocyte response is different in ICAM-4 null mice compared to control mice. We speculate that this may be a reflection of the baseline decrease in island number in the ICAM-4 null mice. Erythroblast enucleation also occurs within the erythroid niche. Earlier, we examined whether abnormal protein sorting during nuclear extrusion creates the deficiencies of membrane proteins that are well described in hereditary spherocytosis (HS) and hereditary elliptocytosis (HE). We observed that whereas glycophorin C partitions to reticulocytes in normal mouse cells, it sorts to extruding nuclei in murine hereditary elliptocytosis cells. Additionally, in a murine model of hereditary spherocytosis, band 3, glycophorin A and RhAG partition to both nuclei and reticulocytes, while in normal cells these three proteins distribute predominantly to reticulocytes. Hence, it appears that abnormal protein sorting generates specific protein deficiencies in hereditary elliptocytosis and hereditary spherocytosis.
authors.affiliation: The Red Cell Physiology Laboratory, The New York Blood Center, 310 East 67th Street, New York, NY 10065, USA.
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Joel Anne
authors.initials: JA
authors.lastname: Chasis
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics; D002454:Cell Differentiation; D004612:Elliptocytosis, Hereditary / Q000235:genetics; D004900:Erythroblasts / Q000166:cytology / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D007797:Laminin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012156:Reticulocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology; D013103:Spherocytosis, Hereditary / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D005353:Fibronectins; C548377:ICAM-4 protein, mouse; D007797:Laminin