Local Myo9b RhoGAP activity regulates cell motility
| Autor: | Birgit Lohmann, Veith Vollmer, Muna Taha, Vera Schwarz, Ulrike Honnert, Martin Bähler, Hans-Joachim Schnittler, Sandra A. Hemkemeyer |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
RHOA cell migration RAC1 myosin macromolecular substances Myosins Cell morphology Biochemistry GEF guanine nucleotide exchange factor GAP GTPase-activating protein 03 medical and health sciences Cell Movement Humans HL-60 cells Pseudopodia Molecular Biology Cells Cultured Actin Myo9b 030102 biochemistry & molecular biology biology Chemistry Macrophages GTPase-Activating Proteins RhoA Cell migration Cell Biology Actin cytoskeleton Cell biology Actin Cytoskeleton 030104 developmental biology lamellipodia RhoGAP biology.protein FCS fetal bovine serum Guanine nucleotide exchange factor Lamellipodium actin DIC differential interface contrast Rac1 Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.013623 |
| Popis: | To migrate, cells assume a polarized morphology, extending forward with a leading edge with their trailing edge retracting back toward the cell body. Both cell extension and retraction critically depend on the organization and dynamics of the actin cytoskeleton, and the small, monomeric GTPases Rac and Rho are important regulators of actin. Activation of Rac induces actin polymerization and cell extension, whereas activation of Rho enhances acto-myosin II contractility and cell retraction. To coordinate migration, these processes must be carefully regulated. The myosin Myo9b, a Rho GTPase-activating protein (GAP), negatively regulates Rho activity and deletion of Myo9b in leukocytes impairs cell migration through increased Rho activity. However, it is not known whether cell motility is regulated by global or local inhibition of Rho activity by Myo9b. Here, we addressed this question by using Myo9b-deficient macrophage-like cells that expressed different recombinant Myo9b constructs. We found that Myo9b accumulates in lamellipodial extensions generated by Rac-induced actin polymerization as a function of its motor activity. Deletion of Myo9b in HL-60-derived macrophages altered cell morphology and impaired cell migration. Reintroduction of Myo9b or Myo9b motor and GAP mutants revealed that local GAP activity rescues cell morphology and migration. In summary, Rac activation leads to actin polymerization and recruitment of Myo9b, which locally inhibits Rho activity to enhance directional cell migration. |
| Databáze: | OpenAIRE |
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