Partial depletion of gamma-actin suppresses microtubule dynamics.

ABSTRACT: Actin and microtubule interactions are important for many cellular events, however these interactions are poorly described. Alterations in ?-actin are associated with diseases such as hearing loss and cancer. Functional investigations demonstrated that partial depletion of ?-actin affects cell polarity and induces resistance to microtubule-targeted agents. To determine whether ?-actin alterations directly affect microtubule dynamics, microtubule dynamic instability was analyzed in living cells following partial siRNA depletion of ?-actin. Partial depletion of ?-actin suppresses interphase microtubule dynamics by 17.5% due to a decrease in microtubule shortening rates and an increase in microtubule attenuation. ?-Actin partial depletion also increased distance-based microtubule catastrophe and rescue frequencies. In addition, knockdown of ?-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 ?-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 ?-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 ?-actin depleted cells (8.5%). Therefore, suppression of microtubule dynamics by partial depletion of ?-actin is associated with marked delays in metaphase-anaphase transition and not mitotic arrest. This is the first demonstration that ?-actin can modulate microtubule dynamics by reducing the microtubule shortening rate, promoting paused/attenuated microtubules, and increasing transition frequencies suggesting a mechanistic link between ?-actin and microtubules.

SUBMITTER: Po'uha ST 

PROVIDER: S-EPMC3613743 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature