A novel role for the cytoskeletal linker protein dystonin in the maintenance of microtubule stability and the regulation of ER-Golgi transport.

Crosslinking proteins maintain organelle structure and facilitate their function through the crosslinking of cytoskeletal elements. We recently found an interaction between the giant crosslinking protein dystonin-a2 and the microtubule-associated protein-1B (MAP1B), occurring in the centrosomal region of the cell. In addition, we showed that this interaction is necessary to maintain microtubule acetylation. Loss of dystonin-a2 disrupts MT stability, Golgi organization, and flux through the secretory pathway. This, coupled to our recent finding that dystonin-a2 is critical in maintaining endoplasmic reticulum (ER) structure and function, provides novel insight into the importance of dystonin in maintenance of organelle structure and in facilitating intracellular transport. These results highlight the importance of cytoskeletal dynamics in communicating signals between organelle membranes and the cytoskeleton. Importantly, they demonstrate how defects in cytoskeletal dynamics can translate into a failure of vesicular trafficking associated with neurodegenerative disease.