Expression of basic fibroblast growth factor isoforms in postmitotic sympathetic neurons: synthesis, intracellular localization and involvement in karyokinesis.

ABSTRACT

Low and high molecular weight isoforms of the mitogen and multifunctional cytokine basic fibroblast growth factor (FGF-2) are up-regulated in neurons and glial cells in response to peripheral nerve lesion. While synthesis, regulation and functions of FGF-2 in non-neuronal cells are well established, the significance of neuronal FGF-2 remains to be investigated in the peripheral nervous system. Therefore, the expression, intracellular localization and possible effects of FGF-2 isoforms were analyzed in primary sympathetic neurons derived from the rat superior cervical ganglion. FGF-2 is detected in the nucleus and in perinuclear Golgi fields of early postnatal neurons which also express mRNA and protein for the FGF receptor type 1. Biolistic transfection of plasmids encoding FGF-2 isoforms fused to fluorescent proteins demonstrates nuclear targeting of 18 kDa FGF-2 and 23 kDa FGF-2 with prominent accumulation in the nucleolus of neurons. Neither overexpression nor treatment with FGF-2 isoforms promotes survival of sympathetic neurons deprived of nerve growth factor; however, neuronal transfection of the high molecular weight FGF-2 isoform in dissociated and slice cultures results in a bi- or multinuclear phenotype. The present study provides evidence for neuronal synthesis and targeting of FGF-2 to the nucleus and Golgi apparatus supporting a dual role of FGF-2 in the nucleus and secretory pathway of sympathetic neurons.