EXPRESSION OF TERMININ IN THE RAT-BRAIN DURING NEURONAL DIFFERENTIATION

Terminin is a cytoplasmic protein originally found in senescent cultured human fibroblasts. In the present study, we investigated terminin expression during development in three brain regions: the cerebral cortex, the neural retina and the cerebellum of the rat brain. By immunocytochemistry we found that terminin immunoreactivity in the brain is mainly localized in neurons. Immunoreactivity to terminin antibody was first noticed in the brain as early as embryonic day 15, and the staining intensity in the cerebral cortex reached maximum level at the first postnatal week, when the cerebral neurons become postmitotic and their synaptic connections with target cells are established. A similar pattern of terminin development was seen in the neural retinas of the same animals as well. Biochemical characterization shows that the anti-terminin antibody recognizes a 90 kDa (Tp90) and a 60 kDa (Tp60) polypeptide in immunoblots of the detergent insoluble fraction of rat brains, while Tp90 was found in the detergent-soluble fraction. Both the Tp90 and Tp60 polypeptides appeared at embryonic day 15 and reached highest levels at postnatal day 1. With the advance of further neural differentiation, however, Tp90 in the detergent-insoluble fraction diminished, and remained only in the detergent-soluble fraction. In the detergent insoluble fraction Tp60 became the predominant species during the first postnatal week. In the cerebellum, where neuronal differentiation is known to be relatively late, quantitative densitometric measurement of terminin abundance on the immunoblots showed that Tp60 in the detergent-insoluble fraction was the predominant form in the second week. Thus, the appearance of a predominant Tp60 coincided with terminal neuronal differentiation. The up-regulation of Tp60, the cell senescence-related form of terminin, as well as a possible increase in solubility of Tp90 when neuronal terminal differentiation takes place, suggest that terminin expression may be involved in the regulation of neuronal differentiation.