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

Miho Taniguchi,Naoto Kobayashi,Fumihiko Hamada,Seiji Matsuda,Hiroaki Nabeka,Kimiko Yamamiya,Hiroyuki Wakisaka,Takuya Doihara,Md Sakirul Islam Khan,Farzana Islam,Tetsuya Shimokawa,Tudor C Badea

doi:10.1371/journal.pone.0255958

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.

Highlights

Prosaposin (PSAP) is a potent trophic factor and precursor of saposins A–D [1,2] (Fig 1)
In the present study, using specific antibodies against PSAP, its receptors, and sortilin [28], we investigated the distribution of PSAP and its receptors in the rat dorsal root ganglion (DRG) during development
To distinguish the distribution of PSAP from that of saposins, an anti-PSAP-specific antibody (IM-1) was generated against a synthetic oligopeptide corresponding to the proteolytic portion of PSAP (Fig 1)

Summary

Introduction

Prosaposin (PSAP) is a potent trophic factor and precursor of saposins A–D [1,2] (Fig 1). PSAP has been identified in various secretory fluids, such as milk, cerebrospinal fluid, and seminal fluid [6,7,8,9,10,11,12,13], suggesting that it serves as a precursor of saposins and as a secretory protein [14]. PSAP has been shown to act as a potent neurotrophic factor, protecting neural cells against cellular damage [15,16,17,18,19,20].

Methods

Results

Conclusion