Partial depletion of gamma‐actin suppresses microtubule dynamics

Actin and microtubule interactions are important for many cellular events, however these interactions are poorly described. Alterations in γ‐actin are associated with diseases such as hearing loss and cancer. Functional investigations demonstrated that partial depletion of γ‐actin affects cell polarity and induces resistance to microtubule‐targeted agents. To determine whether γ‐actin alterations directly affect microtubule dynamics, microtubule dynamic instability was analyzed in living cells following partial siRNA depletion of γ‐actin. Partial depletion of γ‐actin suppresses interphase microtubule dynamics by 17.5% due to a decrease in microtubule shortening rates and an increase in microtubule attenuation. γ‐Actin partial depletion also increased distance‐based microtubule catastrophe and rescue frequencies. In addition, knockdown of γ‐actin delayed mitotic progression, partially blocking metaphase–anaphase transition and inhibiting cell proliferation. Interestingly, in the presence of paclitaxel, interphase microtubule dynamics were further suppressed by 24.4% in the γ‐actin knockdown cells, which is comparable to 28.8% suppression observed in the control siRNA treated cells. Paclitaxel blocked metaphase–anaphase transition in both the γ‐actin knockdown cells and the control siRNA cells. However, the extent of mitotic arrest was much higher in the control cells (28.4%), compared to the γ‐actin depleted cells (8.5%). Therefore, suppression of microtubule dynamics by partial depletion of γ‐actin is associated with marked delays in metaphase‐anaphase transition and not mitotic arrest. This is the first demonstration that γ‐actin can modulate microtubule dynamics by reducing the microtubule shortening rate, promoting paused/attenuated microtubules, and increasing transition frequencies suggesting a mechanistic link between γ‐actin and microtubules. © 2013 Wiley Periodicals, Inc