Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane-cytoskeleton remodeling
Autor: | Siham Boukour, Ted S. Strom, Gregory A. Voth, Najet Debili, Francisco X. Vázquez, Lining Ju, David R. Myers, Jorie Aardema, Hilary Christensen, Arinola Awomolo, Cheng Zhu, Seth J. Corey, Wilbur A. Lam, Reginald Tran, Yolande Chen, David J. Rawlings, Sayali Kale, Walter H. A. Kahr, David Reece, Elisabeth G. Blanchard, Zakary L. Whichard, Brian Chang |
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Rok vydání: | 2013 |
Předmět: |
Blood Platelets
Male Membrane Fluidity Immunology Plenary Paper Wiskott-Aldrich Syndrome Protein Neuronal macromolecular substances Biology Biochemistry Cell Line Colony-Forming Units Assay Minor Histocompatibility Antigens Mice Membrane fluidity Animals BAR domain Cytoskeleton Mice Knockout Ploidies Membrane tubulation Stem Cells fungi Cell Membrane Wiskott–Aldrich syndrome protein Cell Biology Hematology Actin cytoskeleton Thrombocytopenia Biomechanical Phenomena Transport protein Cell biology Mice Inbred C57BL Actin Cytoskeleton Protein Transport Cdc42 GTP-Binding Protein Gene Knockdown Techniques biology.protein Megakaryocytes Microtubule-Associated Proteins Gene Deletion |
Zdroj: | Blood. 122:1695-1706 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood-2013-03-484550 |
Popis: | Megakaryocytes generate platelets through extensive reorganization of the cytoskeleton and plasma membrane. Cdc42 interacting protein 4 (CIP4) is an F-BAR protein that localizes to membrane phospholipids through its BAR domain and interacts with Wiskott-Aldrich Syndrome Protein (WASP) via its SRC homology 3 domain. F-BAR proteins promote actin polymerization and membrane tubulation. To study its function, we generated CIP4-null mice that displayed thrombocytopenia similar to that of WAS(-) mice. The number of megakaryocytes and their progenitors was not affected. However, the number of proplatelet protrusions was reduced in CIP4-null, but not WAS(-), megakaryocytes. Electron micrographs of CIP4-null megakaryocytes showed an altered demarcation membrane system. Silencing of CIP4, not WASP, expression resulted in fewer proplatelet-like extensions. Fluorescence anisotropy studies showed that loss of CIP4 resulted in a more rigid membrane. Micropipette aspiration demonstrated decreased cortical actin tension in megakaryocytic cells with reduced CIP4 or WASP protein. These studies support a new biophysical mechanism for platelet biogenesis whereby CIP4 enhances the complex, dynamic reorganization of the plasma membrane (WASP independent) and actin cortex network (as known for WASP and cortical actin) to reduce the work required for generating proplatelets. CIP4 is a new component in the highly coordinated system of megakaryocytic membrane and cytoskeletal remodeling affecting platelet production. |
Databáze: | OpenAIRE |
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