As we have seen, cell motil­ity requires the devel­op­ment of a pro­trud­ing front and a retract­ing rear, namely a polar­i­sa­tion of cell shape. Most cells are unable to polarise in the absence of micro­tubules, point­ing to a cross-talk between the micro­tubule and the actin cytoskele­ton for the devel­op­ment of polar­ity.

The loss of polar­ity of fibrob­lasts when micro­tubules are dis­as­sem­bled by drugs like noco­da­zole is illus­trated in the fol­low­ing movie:

The effect of the micro­tubule inhibitor noco­da­zole on a gold­fish fibrob­last. Note the loss of polar­i­sa­tion of the cell fol­low­ing the depoly­meri­sa­tion of micro­tubules by this drug.

Live cell imag­ing has pro­vided com­pelling evi­dence about where the cross talk between micro­tubules and actin occurs, namely at the focal adhe­sions where the actin cytoskele­ton is linked via trans­mem­brane recep­tors to matrix lig­ands.

In video sequences of cells in which both micro­tubules and sub­strate adhe­sions were labelled with flu­o­res­cent probes a per­sis­tent inter­ac­tion was revealed between micro­tubules and sub­strate adhe­sion sites. Fish fibrob­lasts have proved a use­ful cell model for these stud­ies as they are thin and can be cul­ti­vated and viewed on the micro­scope at room tem­per­a­ture. The same inter­ac­tions between micro­tubules and adhe­sion sites have also been observed in other cell types.

Exam­ples of the directed growth of micro­tubules into adhe­sion foci (referred to as tar­get­ing) are pre­sented in the next three videos:

Tar­get­ing of sub­strate adhe­sions by micro­tubules. Video of a fish fibrob­last that was co-injected with Cy-3 tubu­lin and rho­damine vin­culin to ren­der both micro­tubules and sub­strate adhe­sions vis­i­ble in the same flu­o­res­cent chan­nel. Note that the micro­tubules grow towards the advanc­ing cell front. As they do so, some pass over, or into adhe­sion foci. (From Kave­rina et al., 1998)

Inset region of the pre­vi­ous movie, show­ing details of microtubule-adhesion site tar­get­ing inter­ac­tions. Three adhe­sion sites are num­bered (1,2,3). Note that the micro­tubules specf­i­cally tar­get the adhe­sion sites by grow­ing into them. In some cases, micro­tubules depoly­merise away from one adhe­sion site and are then redi­rected into another adhe­sion site. (From Kave­rina et al., 1998)

Video of a fish fibrob­last that was trans­fected with GFP-tubulin and Ds-Red zyxin (to label adhe­sion sites) and imaged alter­nately in the green and red flu­o­res­cent chan­nels. Microtubule-adhesion site tar­get­ing inter­ac­tions are cir­cled. (From Small et al., 2002)

Adhe­sion sites can expe­ri­ence mul­ti­ple tar­get­ing inter­ac­tions, either involv­ing sev­eral micro­tubules, repeated tar­get­ing by the same micro­tubule, or a com­bi­na­tion of these events. Micro­tubules can also with­draw from one adhe­sion and redi­rect their growth into another (see videos).

Related Pub­li­ca­tions

  • Kave­rina, I., Rot­tner, K., Small, J. V. (1998). Tar­get­ing, cap­ture, and sta­bi­liza­tion of micro­tubules at early focal adhe­sions. J. Cell Biol. 142, 181190. PDF
  • Small, J. V., Geiger, B., Kave­rina, I., Ber­shad­sky, A. (2002). How do micro­tubules guide migrat­ing cells? Nat. Rev. Mol. Cell Biol. 3, 957964. PDF