The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice

• Published in: PloS one 2012-02, Vol.7 (2), p.e31854-e31854
• Main Authors: Suzuki, Mai, Tanaka, Hirokazu, Tanimura, Akira, Tanabe, Kenji, Oe, Natsuko, Rai, Shinya, Kon, Syunsuke, Fukumoto, Manabu, Takei, Kohji, Abe, Takaya, Matsumura, Itaru, Kanakura, Yuzuru, Watanabe, Toshio
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Anemia; Anemia - pathology; Animals; Assembly; Biology; Bone marrow; Budding; Cell Differentiation; Clathrin; Cloning; Crosses, Genetic; Dentistry; Embryo fibroblasts; Embryo, Mammalian - cytology; Endocytosis; Erythroblasts - cytology; Erythroblasts - metabolism; Erythroid cells; Erythroid Cells - cytology; Erythroid Cells - metabolism; Female; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Flow Cytometry; Fusion protein; Gene Targeting; Genetic engineering; Genotype; Hematology; Hematopoiesis; Humanities; Immunoglobulins; In vivo methods and tests; Internal medicine; Internalization; Iron; Iron - metabolism; Iron content; Leukemia; Lipid monolayers; Liver transplants; Longevity; Male; Maturation; Medicine; Membrane vesicles; Mice; Mice, Inbred C57BL; Mice, Knockout; Monomeric Clathrin Assembly Proteins; Monomolecular films; Mutation; Myeloid leukemia; Neurosciences; Pharmaceutical sciences; Phosphatidylinositol; Physiological aspects; Protein binding; Proteins; Stem cell transplantation; Transferrin; Transferrin - metabolism; Transferrins; Translocation; Tumors; University graduates; Women
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031854

Phosphatidylinositol binding clathrin assembly protein (PICALM), also known as clathrin assembly lymphoid myeloid leukemia protein (CALM), was originally isolated as part of the fusion gene CALM/AF10, which results from the chromosomal translocation t(10;11)(p13;q14). CALM is sufficient to drive clathrin assembly in vitro on lipid monolayers and regulates clathrin-coated budding and the size and shape of the vesicles at the plasma membrane. However, the physiological role of CALM has yet to be elucidated. Here, the role of CALM in vivo was investigated using CALM-deficient mice. CALM-deficient mice exhibited retarded growth in utero and were dwarfed throughout their shortened life-spans. Moreover, CALM-deficient mice suffered from severe anemia, and the maturation and iron content in erythroid precursors were severely impaired. CALM-deficient erythroid cells and embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of transferrin. These results indicate that CALM is required for erythroid maturation and transferrin internalization in mice.