The expression of prosaposin and its receptors, GRP37 and GPR37L1, are increased in the developing dorsal root ganglion

Abstract

Prosaposin (PSAP), a highly conserved glycoprotein, is a precursor of saposins A–D. Accumulating evidence suggests that PSAP is a neurotrophic factor, as well as a regulator of lysosomal enzymes. Recently, the orphan G-protein-coupled receptors GPR37 and GPR37L1 were recognized as PSAP receptors, but their functions have not yet been clarified. In this study, we examined the distribution of PSAP and its receptors in the dorsal root ganglion (DRG) during development using specific antibodies, and showed that PSAP accumulates primarily in lysosomes and is dispersed throughout the cytoplasm of satellite cells. Later, PSAP colocalized with two receptors in satellite cells, and formed a characteristic ring shape approximately 8 weeks after birth, during a period of rapid DRG development. This ring shape, which was only observed around larger neurons, is evidence that several satellite cells are synchronously activated. We found that sortilin, a transporter of a wide variety of intracellular proteins containing PSAP, is strongly localized to the inner side of satellite cells, which contact the neuronal surface. These findings suggest that PSAP and GPR37/GPR37L1 play a role in activating both satellite and nerve cells.

SpatialScope: A unified approach for integrating spatial and single-cell transcriptomics data using deep generative models

“…5g). Astrocytes are reported to have neuroprotective effects on neurons through the Gpr37l1 pathway [52, 53], supporting the cell-cell interactions we identified in the corrected data; In contrast, raw Slide-seq data was too sparse to detect this (Fig. 5h-i).…”

Tracking of Prosaposin, a Saposin Precursor, in Rat Testis

“…Using this specific antibody to the proteolytic portion of PSAP, we described its immunoreactivity as PSAP-IR. 19,24–26…”

“…Using this specific antibody to the proteolytic portion of PSAP, we described its immunoreactivity as PSAP-IR. 19,[24][25][26] A commercial antibody to microtubule-associated protein 2 (MAP2) (Abnova, Taipei, Taiwan) was used because MAP2 was reported to be localized to the cytoplasm of primary and secondary spermatocytes. 27 A commercial antibody to sortilin (EMD Millipore Corp, Billerica, MA) was used because lysosomal trafficking of saposins is mediated by sortilin.…”

“…27 A commercial antibody to sortilin (EMD Millipore Corp, Billerica, MA) was used because lysosomal trafficking of saposins is mediated by sortilin. 25,26,28,29 Immunoblotting Testes were sonicated in lysis buffer [1:5 w/v; 50 mM Tris, 150 mM NaCl, 1 mM ethylenediaminetetraacetic acid (EDTA), 0.1% sodium dodecyl sulfate (SDS), 0.25% sodium deoxycholate, 1% NP-40, pH 7.4] containing NaVO 3 (0.5%), 1% protease inhibitor cocktail (Nacalai Tesque, Kyoto, Japan), and 1% phosphatase inhibitor cocktail (Nacalai Tesque) for 2 min. All procedures were performed on ice.…”

Orphan G Protein-Coupled Receptor GPR37 as an Emerging Therapeutic Target

“…141 Moreover, in facial nerve transection, PSAP and GPR37 were shown to produce neurotrophic factors involved in neuronal repair in microglial and astrocytes. 142,143 Saposin C and its neuroactive fragment TX14A (Figure 3) were specifically associated with the neuroprotective effects of GPR37-expressing astrocytes on neurons subjected to oxidative stress. 48 The administration of TX14A in GPR37-transfected cells induced a dose-dependent increase of luciferase activity with an EC 50 of 19.4 nM.…”