Rapid Degradation of Newly Synthesized Tubulin in Lithium‐Treated Sensory Neurons

When cultured chick sensory neurons were labeled with [ 35 S]methionine for 1 h or longer in the presence of 5–25 m M LiCl, we found a dose‐dependent reduction in the level of radiolabeled tubulin, to one third of control levels, with no noticeable effect on other proteins. The magnitude of this response was identical after a 1‐h or 72‐h preincubation in 25 m M LiCl and returned to control values within 1 h after removal of LiCl. Short (5‐min) pulse‐chase experiments revealed that tubulin synthesis was not affected by Li + , but that newly synthesized tubulin was rapidly degraded, such that 50% of the labeled β‐tubulin was lost within 5 min. There was no enhanced degradation of tubulin present before exposure to Li + . Addition of LiCl at various times before and after a 10‐min pulse suggested that tubulin becomes completely refractory to Li + ‐induced degradation within 10 min after translation. Although Li + treatment resulted in a decrease in the fraction of extant tubulin present in the unassembled form, the Li + ‐induced degradation of nascent tubulin is not a consequence of shifts in assembly state, because colcemid or taxol treatment did not lead to rapid degradation of newly synthesized tubulin, and neither drug altered the response to Li + . We suggest that Li + interferes with the corre ct folding of tubulin polypeptides, exposing sites, normally hidden, to the action of a protease(s).