RASSF1A regulates microtubule dynamics and Golgi integrity
Mol Biol Cell. 2014 Mar;25(6):800-10. doi: 10.1091/mbc.E13-07-0374. Epub 2014 Jan29.
Microtubule segment stabilization by RASSF1A is required for proper microtubule
dynamics and Golgi integrity.
Arnette C(1), Efimova N, Zhu X, Clark GJ, Kaverina I.
Author information:
(1)Department of Cell and Developmental Biology, Vanderbilt University Medical
Center, Nashville, TN 37232 JG Brown Cancer Center, University of Louisville,
Louisville, KY 40202.
Fig. The effect of RASSF1A binding on the microtubule network in RPE cells. Low RASSF1A binding (bottom cell) allows for the formation of a polarized microtubule network; however, high expression (top cell), leads to bundling and kinking of the microtubule network. False colored. Microtubules are shown in magenta. RASSF1A is shown in blue. The Golgi is shown in yellow.
The tumor suppressor and microtubule-associated protein Ras association domain
family 1A (RASSF1A) has a major effect on many cellular processes, such as cell
cycle progression and apoptosis. RASSF1A expression is frequently silenced in
cancer and is associated with increased metastasis. Therefore we tested the
hypothesis that RASSF1A regulates microtubule organization and dynamics in
interphase cells, as well as its effect on Golgi integrity and cell polarity. Our
results show that RASSF1A uses a unique microtubule-binding pattern to promote
site-specific microtubule rescues, and loss of RASSF1A leads to decreased
microtubule stability. Furthermore, RASSF1A-associated stable microtubule
segments are necessary to prevent Golgi fragmentation and dispersal in cancer
cells and maintain a polarized cell front. These results indicate that RASSF1A is
a key regulator in the fine tuning of microtubule dynamics in interphase cells
and proper Golgi organization and cell polarity.
PMCID: PMC3952850 [Available on 2014/5/30]
PMID: 24478455 [PubMed – in process]