Ranvier nodes are flanked by paranodal regions, at the level of which oligodendrocytes or Schwann cells interact closely with axons. Paranodes play a critical role in the physiological properties of myelinated nerve fibers. Paranodin, a prominent 180 kDa transmembrane neuronal glycoprotein, was purified and cloned from adult rat brain, and found to be highly concentrated in axonal membranes at their junction with myelinating glial cells, in paranodes of central and peripheral nerve fibers. The large extracellular domain of paranodin is related to neurexins, and its short intracellular tail binds protein 4.1, a cytoskeleton-anchoring protein. Paranodin may be a critical component of the macromolecular complex involved in the tight interactions between axons and myelinating glial cells characteristic of the paranodal region.

Focal adhesion kinase (pp125FAK, FAK) is a 125 kDa non-receptor tyrosine kinase enriched in focal adhesions of various cell types, where it is thought to transduce signals triggered by contact with the extracellular matrix. We have studied the expression and localization of FAK in rat CNS. Immunoblotting, immunohistochemistry and in situ hybridization revealed the presence of FAK in all regions of the adult brain and demonstrated its enrichment in specific neuronal populations of the cerebral and cerebellar cortex, as well as in the hippocampus. During development, FAK protein levels were highest around birth in cerebral cortex and caudate putamen and decreased in the adult. In situ hybridization revealed enrichment of FAK mRNA in the ventricular germinative and external layers during the last period of embryonic growth. In primary cultures FAK immunoreactivity was localized in focal adhesions in astrocytes, whereas in developing neurons the highest levels were found in growth cones and perikarya. In the growth cone, FAK immunoreactivity colocalized with actin filaments. In mature neurons FAK appeared to be distributed in the whole cytoplasm, with no enrichment in any cellular compartment. Our results demonstrate the presence of high levels of FAK in rat CNS, maximal during development but persistent in the adult. Its enrichment in growth cones suggests that it may play a role in neurite outgrowth, as well as in plasticity in the adult.

No abstract