Abstract:Prosaposin (PSAP), a highly conserved glycoprotein, is a precursor of saposins A–D. Accumulating evidence suggests that PSAP is a neurotrophic factor that induces differentiation and prevents death in a variety of neuronal cells through the active region within the saposin C domain both in vivo and in vitro. Recently, GPR37 and GPR37L1 were recognized as PSAP receptors. In this study, we examined the alteration in expression of PSAP and its receptors in the cerebellum using rats injected with kainic acid (KA).… Show more
“…The specificity of the GPR37 and GPR37L1 antibodies used in this study was examined in the mice cerebellum by western blotting. A single immunoreactive band, similar to the report by Li et al [ 26 ], was observed for each antibody ( Fig. 1 Fig.…”
G protein-coupled receptor (GPR) 37 and GPR37L1 are known to modulate the dopaminergic neuron activity, and recently, they are identified as candidate prosaposin receptors. Intercellular prosaposin is proteolytically processed into four saposins, each of which acts as a sphingolipid hydrolase activator in the lysosome. In contrast, extracellular prosaposin exerts a trophic effect on neurons via GPR37 and GPR37L1. In this study, the expression patterns of GPR37 and GPR37L1 in the mouse digestive system were examined immunohistochemically. The islets of Langerhans of the pancreas showed intense immunoreactivity for GPR37 and GPR37L1. Weak immunoreactivity for GPR37 and GPR37L1 was found in the nerve plexuses of the esophagus and small and large intestines. Colocalization of GPR37 and tyrosine hydroxylase immunoreactivity was observed in the neuron of the nerve plexus of the large intestine. This study suggests the possibility that prosaposin affects the function of islet-secreting cells. Also, the expression of GPR37 and GPR37L1 in the nerve plexus suggests that prosaposin exerts a trophic effect not only in the central nervous system, but also in the enteric nervous system.
“…The specificity of the GPR37 and GPR37L1 antibodies used in this study was examined in the mice cerebellum by western blotting. A single immunoreactive band, similar to the report by Li et al [ 26 ], was observed for each antibody ( Fig. 1 Fig.…”
G protein-coupled receptor (GPR) 37 and GPR37L1 are known to modulate the dopaminergic neuron activity, and recently, they are identified as candidate prosaposin receptors. Intercellular prosaposin is proteolytically processed into four saposins, each of which acts as a sphingolipid hydrolase activator in the lysosome. In contrast, extracellular prosaposin exerts a trophic effect on neurons via GPR37 and GPR37L1. In this study, the expression patterns of GPR37 and GPR37L1 in the mouse digestive system were examined immunohistochemically. The islets of Langerhans of the pancreas showed intense immunoreactivity for GPR37 and GPR37L1. Weak immunoreactivity for GPR37 and GPR37L1 was found in the nerve plexuses of the esophagus and small and large intestines. Colocalization of GPR37 and tyrosine hydroxylase immunoreactivity was observed in the neuron of the nerve plexus of the large intestine. This study suggests the possibility that prosaposin affects the function of islet-secreting cells. Also, the expression of GPR37 and GPR37L1 in the nerve plexus suggests that prosaposin exerts a trophic effect not only in the central nervous system, but also in the enteric nervous system.
Current protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) often rely on animal co-culture and mostly exist as monolayers, limiting their capability to recapitulate the complex processes in the developing cerebellum. Here, we employed a robust method, without the need for mouse co-culture to generate three-dimensional cerebellar organoids from hPSCs that display hallmarks of in vivo cerebellar development. Single-cell profiling followed by comparison to human and mouse cerebellar atlases revealed the presence and maturity of transcriptionally distinct populations encompassing major cerebellar cell types. Encapsulation with Matrigel aimed to provide more physiologically-relevant conditions through recapitulation of basement-membrane signalling, influenced both growth dynamics and cellular composition of the organoids, altering developmentally relevant gene expression programmes. We identified enrichment of cerebellar disease genes in distinct cell populations in the hPSC-derived cerebellar organoids. These findings ascertain xeno-free human cerebellar organoids as a unique model to gain insight into cerebellar development and its associated disorders.
“…The detection of higher levels of PSAP in PV-positive GABAergic inhibitory interneurons and their axons around pyramidal neurons suggested the axonal transport of PSAP [24,25] (Figure 1h-i). Similarly, PSAP was strongly expressed in the Purkinje cells and interneurons of the cerebellum of KA-injected rats [26]. These findings provide insights into the role of PSAP in alleviating the neural damage caused by KA.…”
Section: Psap Rescues Neurons From Damage Induced By Neurotoxic Agentsmentioning
Prosaposin (PSAP) is both a precursor protein of saposin A-D and a neuroprotective factor. In response to neuropathological disorders such as ischemia, neurotoxins, and nerve transection, PSAP is up-regulated such that both PSAP immunoreactivity and PSAP mRNA levels in neurons increase significantly. PSAP and an 18-mer peptide (PS18) derived from its neurotrophic region were shown to significantly protect damaged neurons. Meyer et al. [1] characterized the PSAP receptors GPR37 and GPR37L1, both of which are involved in neuronal protection, although their expression and their interactions with PSAP have not been fully elucidated (see the review of Smith [2]). However, the increased expression of PSAP and its receptors in damaged neurons and the surrounding glia points to a role for these proteins in protecting damaged cells in the nervous system. This mini-review examines the neuro-and glio-protective functions of PSAP and its receptors, based mainly on data from neuropathological in vivo models. Additional information can be found in the review by Meyer et al. [3].
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