Phosphorylation of Microtubule Proteins in Rat Brain at Different Developmental Stages: Comparison with That Found in Neuronal Cultures

Abstract

The phosphorylation of rat brain microtubule protein on intracranial injection of labeled phosphate has been analyzed. The major microtubule protein components phosphorylated in vivo in rat brain are the high‐molecular‐weight microtubule‐associated proteins (MAPs) MAP‐1A, MAP‐1B, and MAP‐2. A slight phospholabeling of β‐tubulin, which corresponds to the phosphorylation of a minor neuronal β‐tubulin isotype, is also observed. Whereas MAP‐1B, MAP‐2, and β‐tubulin are phosphorylated in the brain of 5‐day‐old rat pups, when most neurons of the CNS are extending processes, MAP‐1A phosphorylation is observed only after neuronal maturation takes place. The phosphorylation of MAP‐1A, MAP‐1B, and β‐tubulin may be due mainly to casein kinase II or a related enzyme, whereas MAP‐2 appears to be modified by other enzymes such as the cyclic AMP‐dependent protein kinase (protein kinase A) and the calcium/ phospholipid‐dependent protein kinase (protein kinase C). Microtubule protein phosphorylation has also been studied in neuronal cultures. In differentiated neuroblastoma cells, only MAP‐1B and β‐tubulin are phosphorylated in a manner coupled to neurite outgrowth. In primary cultures of fetal rat brain neurons, the pattern of microtubule protein phosphorylation resembles that found in vivo in rat pup brain. As phosphorylated MAP‐1A and MAP‐1B are present mainly on assembled microtubules, whereas the phosphorylation of MAP‐2 decreases its interaction with microtubules, a role can be suggested for the phosphorylation of these proteins in the regulation of microtubule assembly and disassembly during neuronal development.