Genetic evidence for concerted control of actin dynamics in cytokinesis, endocytic traffic, and cell motility by coronin and Aip1.
Coronin and actin-interacting protein 1 (Aip1) are actin-binding proteins that by different mechanisms inhibit actin polymerization or enhance the disassembly of actin filaments. Cells of Dictyostelium discoideum lacking both proteins are retarded in growth and early development and often fail to proceed to fruiting body formation. Coronin/Aip1-null cells show numerous surface protrusions enriched in filamentous actin and cofilin. We show that the double-null cells are characterized by an increase in filamentous actin that causes a thickening of the cell cortex. This imbalance has severe consequences for processes that rely on the dynamic reorganization of the actin cytoskeleton, such as cell motility, cytokinesis and endocytosis. Although cell motility is considerably slowed down, the double-mutant cells are still capable of orientating in a gradient of chemoattractant. The cytokinesis defect is caused by the lack of proper cleavage furrow formation, a defect that is partially rescued by low concentrations of latrunculin A, an inhibitor of actin polymerization. Furthermore, we demonstrate that the disassembly of the actin coat after phagocytic or macropinocytic uptake is significantly delayed in the double-mutant cells. Our results prove that coronin and Aip1 are important effectors that act together in maintaining the balance of actin polymerization and depolymerization in living cells.
Ishikawa-Ankerhold
Hellen C
HC
Cell Dynamics, Max Planck Institute of Biochemistry, Martinsried, Germany.
Gerisch
Günther
G
Müller-Taubenberger
Annette
A
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D048749:Cytokinesis / Q000187:drug effects; D004023:Dictyostelium / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000187:drug effects; D008840:Microfilament Proteins / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology; D054378:Acetogenins
D015107:4-Butyrolactone; D051339:Actin Depolymerizing Factors; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008840:Microfilament Proteins; D053778:Thiazolidines; C115237:actin interacting protein 1; C438920:coronin acetogenin; D054378:Acetogenins; C037067:latrunculin A