Type II brain 4.1 (4.1B/KIAA0987), a member of the protein 4.1 family, is localized to neuronal paranodes

Histochemical analyses of type Iii brain 4.1/4.1B/KIAA0987, a member of the protein 4.1 family, were carried out in rat brain. In situ hybridization ( ISH) showed that type II brain 4.1 mRNA is expressed in a variety of neuron al cells. In particular, type II:brain 4.1 mRNA was actively transcribed in the cells of the mesencephalon and the brainstem, which have large myelina ted nerve fibers. Expression of type II brain 4.1 mRNA was not observed at least in glial cells distributed in nerve fiber tracts. In immunohistochemi cal studies using anti-type II brain 4.1-specific antibody, the major immun osignals appeared as brilliant pairs of dots along nerve fibers. Such immun osignals were detected throughout the brain, but were highly concentrated i n nerve fiber tracts. These data suggested that type II brain 4.1 is predom inantly localized to neuronal paranodes. Detailed analysis concentrating on the nodal region indicated that type II brain 4.1 is present at the parano dal membrane but not in the axoplasm. Weaker type II brain 4.1-specific imm unosignals were observed along the internodal membrane of myelinated axons and in the cytoplasm of some neuronal cells. Finally, comparative immunohis tochemical studies using antibodies against the other three protein 4.1 fam ily members, type I brain 4.1/4.1N/KTAA0338, erythroid type 4.1 (4.1R) and 4.1G, demonstrated that each of these proteins is distributed in a unique p attern in the cerebellum. Our results are the first to show that type II br ain 4.1 is the only member of the protein 4.1 family localized to neuronal paranodes. (C) 2000 Elsevier Science B.V. All rights reserved.