Microtubules and cell adhesion complexes

Cells are connected to their surroundings by cell adhesion complexes, collections of interacting proteins that transmit cellular signals between the outside and the inside of the cell. This signalling allows a cell to sense its environment and respond in remarkable ways, such as by moving, secreting proteins or changing into a different type of cell. But how do cell adhesion complexes receive and integrate these cellular signals?

Network of adhesion complex changes upon cytoskeletal disruption

To address aspects of this question, Dan Ng, and other members of Martin Humphries’ lab, set out to assess the influence of the cell’s cytoskeleton on the proteins that form adhesion complexes. Specifically, the dynamic cytoskeletal filaments called microtubules were examined. Microtubules play important roles in transporting molecules around the cell and giving cells their shape and strength, helping them move and allowing them to divide.

It has been known for some time that the microtubule cytoskeleton connects to adhesion complexes, which themselves are linked to integrin signalling receptors at the cell surface, and that these connections affect the protein make up of cell adhesions. But how this protein make up changes under the influence of microtubules was poorly understood.

Dan treated cells with nocodazole, a drug that interferes with microtubule growth. He then isolated the proteins in the cell adhesion complexes and analysed them using proteomics, an approach that measures all the proteins in a system. When microtubules were disrupted, there was an increase in proteins in adhesion complexes. This growth in cell adhesions depended upon forces within the cell, controlled by the contractility of another part of the cytoskeleton, actomyosin, which increases upon microtubule disruption.

This work, which was published in PLoS One, detailed a complex cross-talk between adhesion complexes, microtubules and the cellular forces that they transmit. These findings help us better understand the molecular toolkit that allows cells to sense and respond to their environment.

Funding
This work was supported by the Wellcome Trust.

Citation
Ng et al. Microtubule-dependent modulation of adhesion complex composition. PLoS One 9, e115213 (2014)
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