Microtubules at the Membrane in Apoptosis

by on 21st of November, 2007 in Of Interest

Apoptosis, or programmed cell death, is an evolutionarily conserved and neatly orchestrated process important for tissue remodeling and safe elimination of severely damaged cells. Conducted by a caspase-mediated proteolytic cascade, the cell death program results in a series of cellular changes distinct from cellular necrosis. And one of the critical aspects that distinguish apoptosis from necrosis is that intracellular components of apoptotic cells are isolated, preventing membrane permeability and release of inflammatory molecules.

Just how do dying cells keep themselves from spilling out their materials into the surrounding tissues? And what role do the cytoskeleton components have in this process? Those are the questions that Jos?© S??nchez-Alc??zar and colleagues1 asked in a paper in July’s issue of the journal Apoptosis.

As the authors note in the discussion:

It is well established that the first step in most cells undergoing apoptosis involves a rearrangement of the actomyosin cytoskeleton into a cortical contractile ring in preparation for [membrane] blebbing2. However during the execution phase, these actin filaments depolymerize.

How, then, does the cell continue to isolate its intracellular material during the final stages of cell death? S??nchez-Alc??zar et al. looked at microtubules as one possibility, and found a cortical ring of microtubules, which they describe as the apoptotic microtubule network (AMN).

apoptosis

From Figure 1 – Healthy cell (left) and camptothecin (CPT)-treated cell in apoptosis (right). Beta-Tubulin (green), Active Caspase-3 (red) and Hoechst-stained DNA (blue) are shown. If you click on the image, the healthy cells are on the top row, with CPT-treated cells on the bottom row.

Moreover, the authors also found that disruption of the AMN with colchicine disrupted the AMN, and increased plasma membrane permeability as suggested by necrotic release of lactic dehydrogenase.

  1. S??nchez-Alc??zar JA, et al. The apoptotic microtubule network preserves plasma membrane integrity during the execution phase of apoptosis. Apoptosis. 2007 Jul;12(7):1195-208. doi:10.1007/s10495-006-0044-6
  2. Mills JC, Stone NL, Pitman RN. Extranuclear apoptosis: The role of the cytoplasm in the execution phase. J Cell Biol 1999 Aug 23;146(4):703–708.

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