Directional Persistence of Migrating Cells Requires Kif1C-Mediated Stabilization of Trailing Adhesions

• Published in: Developmental cell Vol. 23; no. 6; pp. 1153 - 1166
• Main Authors: Theisen, Ulrike, Straube, Ekkehard, Straube, Anne
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 11.12.2012; Cell Press
• Subjects: Biological and medical sciences; Cell Adhesion - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell Movement - physiology; Cell physiology; Fibroblasts - cytology; Fibroblasts - metabolism; Focal Adhesions - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Integrin alpha5beta1 - metabolism; Kinesin - metabolism; Microtubules - metabolism; Molecular and cellular biology; Myosin Type II - metabolism; Protein Transport; Retinal Pigment Epithelium - cytology; Persistence; Development; Adhesion
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.11.005

Directional cell migration requires the establishment and maintenance of long-term differences in structure and function between the front and back of a cell. Here, we show that the microtubule motor Kif1C contributes to persistent cell migration primarily through stabilization of an extended cell rear. Kif1C-mediated transport of α5β1-integrins is required for the proper maturation of trailing focal adhesions and resistance to tail retraction. Tail retraction precedes and induces changes in migration direction. Stabilization of cell tails through inhibition of myosin II activity suppresses the Kif1C depletion phenotype and results in longer-lived tails and higher directional stability of migrating cells. Taken together, these findings indicate that the maintenance of an extended, tense cell tail facilitates directional migration. We propose a rear drag mechanism for directional persistence of migration whereby the counterforce originating from a well-anchored tail serves to maintain directionality of the force-generating leading edge of the cell. [Display omitted] ► Kif1C delivers integrins to support maturation of trailing adhesions ► Kif1C stabilizes cell tails and supports directionally persistent migration ► Retraction of cell tails precedes and induces directional changes in migration ► Reduction of contractility increases tail stability and directional persistence Theisen et al. show that the microtubule motor Kif1C mediates α5β1-integrin transport for proper maturation of trailing focal adhesions, resistance to tail retraction, and support of directionally persistent cell migration. They propose that directionality of the force-generating cell leading edge is governed by the counterforce originating from a well-anchored tail.