Developmental study of factors controlling microtubule in vitro cold-stability in rat cerebrum

The ability of crude cerebrum supernatant to stabilize, at a low temperature, cold-labile microtubules purified from beef brain was studied during development in the rat. The cold-stabilizing activity of the supernatant was low during the first postnatal week, rose significantly during the second postnatal week, and thereafter continued to increase to the adult level. The partial purification of stable-tubule-only polypeptide (STOP) from the supernatant showed that high amounts of this protein exist at all ages, especially in young animals. The age-related increase in the microtubule cold-stabilizing activity of the cerebrum supernatant resulted from a developmental decrease in factors inhibiting STOP activity. The present study shows that (1) a close temporal correlation exists between the in vitro and in situ acquisition of cold-stable microtubules during brain development, (2) STOP activity may account for this acquisition, and (3) STOP activity is controlled by inhibiting factors that decrease with age, in turn allowing increased stability of the microtubular apparatus, a necessary condition for the development of neuronal processes.