Selective prosaposin expression in Langerhans islets of the mouse pancreas.

The islets of Langerhans are clusters of endocrine cells surrounded by exocrine acinar cells in the pancreas. Prosaposin is a housekeeping protein required for normal lysosomal function, but its expression level is significantly different among tissues. Prosaposin also exists in various body fluids including serum. Intracellularly, prosaposin activates lysosomes and may support autophagy, and extracellularly, prosaposin promotes survival of neurons via G protein-coupled receptors. In this study, prosaposin and its mRNA expression were examined in endocrine cells of the islets as well as in exocrine acinar cells in the pancreas of mice by in situ hybridization and immunostaining. High expression levels of prosaposin were found in Alpha, Beta and Delta cells in the islets, whereas prosaposin mRNA expression was faint or negative and prosaposin immunoreactivity was negative in exocrine acinar cells. The high expression levels of prosaposin in endocrine cells may indicate that prosaposin plays a crucial role in crinophagy, which is a characteristic autophagy in peptide-secreting endocrine cells, and/or that prosaposin is secreted from pancreatic islets. Since prosaposin has been reported in serum, this study suggests a new possible function of the Langerhans islets.

Expression patterns of prosaposin and its receptors, G protein-coupled receptor (GPR) 37 and GPR37L1, in the mouse olfactory organ.

Prosaposin is a glycoprotein conserved widely in vertebrates, because it is a precursor for saposins that are required for normal lysosomal function and thus for autophagy, and acts as a neurotrophic factor. Most tetrapods possess two kinds of olfactory neuroepithelia, namely, the olfactory epithelium (OE) and the vomeronasal epithelium (VNE). This study examined the expression patterns of prosaposin and its candidate receptors, G protein-coupled receptor (GPR) 37 and GPR37L1, in mouse OE and VNE by immunofluorescence and in situ hybridization. Prosaposin immunoreactivity was observed in the olfactory receptor neurons, vomeronasal receptor neurons, Bowman's gland (BG), and Jacobson's gland (JG). Prosaposin expression was mainly observed in mature neurons. Prosaposin mRNA expression was observed not only in these cells but also in the apical region of the VNE. GPR37 and GPR37L1 immunoreactivities were found only in the BG and/or the JG. Prosaposin was suggested to secrete and facilitate the autophagic activities of the neurons and modulate the mucus secretion in mouse olfactory organ.

Expression of prosaposin and its G protein-coupled receptor (GPR) 37 in mouse cochlear and vestibular nuclei.

Prosaposin is a precursor of lysosomal hydrolases activator proteins, saposins, and also acts as a secretory protein that is not processed into saposins. Prosaposin elicits neurotrophic function via G protein-coupled receptor (GPR) 37, and prosaposin deficiency causes abnormal vestibuloauditory end-organ development. In this study, immunohistochemistry was used to examine prosaposin and GPR37 expression patterns in the mouse cochlear and vestibular nuclei. Prosaposin immunoreactivity was observed in neurons and glial cells in both nuclei. GPR37 immunoreactivity was observed in only some neurons, and its immunoreactivity in the vestibular nucleus was weaker than that in the cochlear nucleus. This study suggests a possibility that prosaposin deficiency affects not only the end-organs but also the first center of the vestibuloauditory system.