Repellent and Attractant Guidance Cues Initiate Cell Migration by Distinct Rear-Driven and Front-Driven Cytoskeletal...

Area of Science:

• Cell Biology
• Biophysics

Background:

• Cellular guidance via attractants and repellents is crucial for animal development and disease.
• While attractive cell migration is well-studied, repulsive guidance mechanisms remain less understood.
• The precise initiation mechanism of cell migration in response to guidance cues is debated.

Purpose of the Study:

• To investigate and differentiate the mechanisms by which cells initiate migration in response to attractive versus repulsive cues.
• To test the hypothesis that cell symmetry breaking can be achieved by front protrusion, rear retraction, or both.

Main Methods:

• Utilized the Dictyostelium model system to study cell behavior.
• Applied cyclic AMP (cAMP) as an attractant and its analog 8CPT as a repellent.
• Analyzed cell margin displacement, actin filament assembly, and myosin II dynamics.

Main Results:

• Attractive cue (cAMP) induced symmetry breaking via front protrusion, initiated by actin assembly.
• Repulsive cue (8CPT) induced symmetry breaking via rear retraction, requiring myosin II accumulation.
• Rear retraction in response to 8CPT was independent of myosin II polarization and motor-based contractility.

Conclusions:

• Cellular response to guidance cues involves distinct symmetry-breaking mechanisms: protrusion for attraction and retraction for repulsion.
• Myosin II plays a critical role in repulsive cell guidance by mediating rear retraction.
• These findings reveal a novel concept in understanding cell guidance mechanisms.