Regulation of microtubule-associated protein MAP1B-tubulin interaction by acidic phospholipids

Microtubule-associated protein MAP1B, a major neuronal cytoskeletal protein, is highly expressed during an early stage of brain development and has been shown to be important for normal brain development. Because MAP1B is involved in neurite outgrowth and is concentrated in growth cone membranes, the protein may interact directly with the membrane components. In this study, we showed that MAP1B purified from young rat brain can bind to acidic phospholipids such as phosphatidylserine and phosphatidylinositol, but not to a neutral phospholipid, phosphatidylcholine. Furthermore, the binding of MAP1B to microtubules was inhibited by acidic phospholipids. Phosphatidylcholine showed no effect on the binding of MAP1B to the microtubules. Using synthetic peptides derived from the tubulin-binding domain of MAP1B, the phospholipid-binding site of MAP1B was located to the C-terminal half of the tubulin-binding domain. These results suggest that MAP1B binds to biological membranes through its tubulin-binding site and that the binding may play an important role in the dynamic regulation of cytoskeletons in the growth cone.