the picalm protein plays a key role in iron homeostasis and cell proliferationpicalm蛋白铁体内平衡和细胞增殖中起着关键作用.pdfVIP

The PICALM Protein Plays a Key Role in Iron Homeostasis and Cell Proliferation 1 1 2 1 1 Paula B. Scotland , Jessica L. Heath , Amanda E. Conway , Natasha B. Porter , Michael B. Armstrong , 1 3 1 1,2 Jennifer A. Walker , Mitchell L. Klebig , Catherine P. Lavau , Daniel S. Wechsler * 1 Division of Pediatric Hematology-Oncology, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America Abstract The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM) protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer’s disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM’s function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR) internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clat