Disease relevance of Exoc6

• Reticulocyte iron and transferrin uptake was studied in hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse characterized by hypochromic microcytic anemia, reticulocytosis, hyperferremia, and increased red-cell-free protoporphyrin [1].

High impact information on Exoc6

• A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice [2].
• We propose that inactivation of Sec15l1 alters recycling of transferrin cycle endosomes and increases the release of transferrin receptor exocytic vesicles [2].
• To assess the mutation's effect on hematopoiesis, unfractionated bone marrow (BM) from either a mutant C57BL6/J-hbd/hbd, Gpi1b/Gpi1b (phenotype symbol HBD), or normal C57BL6/J-+hbd/+hbd, Gpi1b/Gpi1b mouse was injected intravenously into irradiated congenic C57BL6/J-+hbd/+hbd, Gpi1a/Gpi1a, lgh(a)/lgh(a), Thy1a/Thy1a mice [3].
• Therefore, the product of Sec15l1 is directly involved in vesicular trafficking, docking, fusing, and/or cargo delivery in erythroid precursors [4].
• MATERIALS AND METHODS: Reticulocytes were harvested from hbd/hbd mice and from background- and age-matched controls [4].

Biological context of Exoc6

• We tested the hypothesis that the mutation causes defective slow or rapid receptor recycling by measuring endocytosis and exocytosis of transferrin by hbd reticulocytes [5].
• OBJECTIVE: To study the effect of persistent hemoglobin-deficit mutation (hbd/hbd) on hematopoiesis and the function of hematopoietic stem cells (HSCs) [6].
• RESULTS: Both young and old hbd/hbd mutants exhibited a microcytic anemia with significantly (p<0.01) lower levels of hemoglobin and mean corpuscular volume [6].
• There were significant declines in CD45R+ B cells in both blood (p<0.01) and BM (p<0.05) in old hbd/hbd mice, suggesting that B-cell homeostasis was compromised [6].
• METHODS: Young and old mice homozygous for the spontaneous hbd/hbd mutation were compared to young and old wild-type control mice, all on the C57BL/6 background, over cellular composition in blood and bone marrow (BM) using cell counting, complete blood counts, and flow cytometry [6].

Anatomical context of Exoc6

• Finally, utilization of endosomal radioiron was likewise deficient in the hbd reticulocytes [4].
• The recently identified gene responsible, Sec15l1, is specific to hematopoietic stem cells and is homologous to a gene encoding a member of the exocyst pathway in yeast [4].
• CONCLUSION: Persistent hbd/hbd mutation causes hematopoiesis defects in the B cell lineage [6].
• These findings suggest that hbd/hbd reticulocytes have a defect in iron acquisition that is distal to the binding of transferrin to the cell membrane receptor [1].

Associations of Exoc6 with chemical compounds

• We also found that +/+ and hbd reticulocytes take up free, ferrous iron at identical rates, while the rates of Tf internalization and externalization were significantly decreased in the mutant cells [4].

Other interactions of Exoc6

• Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking [7].

References