Excess centrosomes disrupt endothelial cell migration via centrosome scattering

Area of Science:

• Cell Biology
• Molecular Biology
• Pathology

Background:

• Supernumerary centrosomes are known to cause mitotic errors like aneuploidy.
• The impact of extra centrosomes during the interphase stage of the cell cycle remains largely uncharacterized.

Purpose of the Study:

• To investigate the interphase effects of supernumerary centrosomes in endothelial cells.
• To understand the molecular mechanisms linking excess centrosomes to cellular dysfunction and potential pathologies.

Main Methods:

• Analysis of interphase endothelial cells with varying centrosome numbers.
• Assessment of cell migration, blood vessel sprouting, microtubule nucleation, Golgi integrity, and vesicle trafficking.
• Investigation of centrosome-localized gamma-tubulin and the role of Plk1 in regulating microtubule dynamics.

Main Results:

• Even one extra centrosome in interphase endothelial cells led to increased centrosome scattering and reduced microtubule nucleation capacity.
• These defects correlated with compromised Golgi integrity and randomized vesicle trafficking.
• Ablation of excess centrosomes partially rescued these cellular parameters, and Plk1 activity influenced centrosome-localized gamma-tubulin levels and dynamics.

Conclusions:

• Centrosome-microtubule interactions during interphase are crucial for maintaining centrosome clustering and cell polarity.
• Disruption of interphase cell behavior by supernumerary centrosomes contributes to disease independently of mitotic defects.