Distribution of semaphorin IV in adult human brain

The semaphorins comprise a family of secreted and membrane bound proteins that influence development of the nervous system as well as non-neural organs. H.SemaIV was originally isolated from a homozygously deleted region involving a subset of small cell lung cancers, a neuroendocrine derived neoplasm. To investigate H.SemaIV expression, specific polyclonal antibodies directed against a unique polypeptide (amino acids 758-773) were developed and their specificity confirmed. In cell lines, H.SemaIV staining was observed in cytoplasmic granules. In the normal adult human brain, we noted three general characteristics of H.SemaIV expression. H.SemaIV was strongly present in specific nuclei or in neuronal regions arranged in defined subnuclear structures. It was also present in neurons but not glial cells or ependymocytes. Lastly, H.SemaIV was not present in cell bodies, but rather in fibers and nerve terminals. Interestingly, an altered pattern of staining was detected in brains of three patients with Alzheimer's disease.