Neuroendocrine-specific protein (NSP) reticulons are expressed in neur
al and neuroendocrine tissues and cell cultures derived therefrom, whi
le most other cell types lack NSP-reticulons. Three major subtypes hav
e been identified so far, designated NSP-A, NSP-B, and NSP-C. We have
investigated the correlation between the degree of neuronal differenti
ation, determined by morphological and biochemical criteria, and NSP-r
eticulon subtype expression. For this purpose, several human neuroblas
toma cell lines, exhibiting different degrees of neuronal differentiat
ion, were examined immuno(cyto) chemically. It became obvious that the
expression of NSP-C, as detected by immunofluorescence microscopy and
Western blotting, is most prominent in cell lines with a high degree
of neuronal differentiation, such as LA-N-5. Such highly differentiate
d cells also express other neural and neuroendocrine markers, such as
neural cell adhesion molecule (NCAM), neurofilament proteins, synaptop
hysin, and chromogranin. NSP-A was observed in all cell lines to a dif
ferent extent. However, no clear correlation was observed with the deg
ree of neuronal differentiation as defined by other neuronal and neuro
endocrine markers or morphology. NSP-B could not be detected. The indu
ction of neuronal differentiation with nerve growth factor, dbcAMP, an
d retinoic acid in the rat pheochromocytoma cell line PC12 and the hum
an teratocarcinoma cell line hNT2, respectively, induced the expressio
n of NSP-A and NSP-C in these cell lines parallel to the induction of
neurofilament protein expression. It is concluded that NSP-C expressio
n, in particular, is strongly correlated with neuronal differentiation
.