Dystrophin, the protein absent in Duchenne muscular dystrophy, is better at networking than researchers realized. The protein's links to two kinds of cytoskeletal components are well known, and now Prins et al. demonstrate that dystrophin also fastens to microtubules.
With its fragile plasma membrane, a muscle cell lacking dystrophin can die from mechanical stress. Although dystrophin is a middleweight in comparison, it resembles the heavyweight cytolinker proteins that keep cells in shape by hitching membrane-spanning proteins to the cytoskeleton. Previous studies have shown that it hooks up with transmembrane proteins and two parts of the cytoskeleton—intermediate filaments and actin—but researchers haven't demonstrated a connection to microtubules.
Prins et al. showed that dystrophin and microtubules coincide at costameres, portions of the cytoskeleton that reinforce the plasma membrane in muscle cells. The researchers also observed that microtubules and dystrophin sediment together if dystrophin sports a putative microtubule-binding domain, but not if the domain is missing. Dystrophin also stabilizes microtubules forced to depolymerize by cold. And when cells lack the protein, microtubule networks snarl.
The findings suggest that dystrophin does function like the cytolinkers, providing structural support for muscle cells in part by stabilizing or organizing microtubules. As a result, muddled microtubules might be responsible for some of the defects of muscular dystrophy.
