14-3-3 proteins tune non-muscle myosin II assembly

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• The 14-3-3 protein family is essential and highly conserved across eukaryotes.
• Overexpression of specific 14-3-3 proteins is linked to increased metastatic potential in various cancers.
• In Dictyostelium, 14-3-3 influences myosin II turnover, cortical tension, cell shape, and cytokinesis.

Purpose of the Study:

• To investigate the interaction mechanism between 14-3-3 proteins and myosin II.
• To determine how 14-3-3 proteins regulate myosin II assembly.
• To explore the evolutionary conservation of this regulatory mechanism.

Main Methods:

• In vitro and in vivo studies using Dictyostelium and human proteins.
• Purified myosin II tail fragments and 14-3-3 proteins were used in assembly assays.
• Investigated direct interaction and phosphorylation dependence.

Main Results:

• The interaction between 14-3-3 proteins and myosin II is direct and phosphorylation-independent.
• All seven human 14-3-3 proteins modulated the assembly of at least one myosin II paralog.
• Demonstrated a conserved mechanism of myosin II assembly regulation across species.

Conclusions:

• 14-3-3 proteins directly regulate myosin II assembly through a conserved mechanism.
• Altered 14-3-3 expression in humans may inhibit the tumor suppressor myosin II.
• This regulation contributes to altered cell mechanics in metastatic cancers.