Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection.

Joji Kunihiro,Takuya Doihara,Shouichiro Saito,Kana Unuma,Md Sakirul Islam Khan,Hiroyuki Wakisaka,Seiji Matsuda,Fumihiko Hamada,Kimiko Yamamiya,Tetsuya Shimokawa,Hiroaki Nabeka,Farzana Islam,Faramarz Dehghani

doi:10.1371/journal.pone.0241315

Joji Kunihiro, Takuya Doihara + Show 11 more

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https://doi.org/10.1371/journal.pone.0241315

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Abstract

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

Highlights

Prosaposin (PS) is the precursor protein of four small lysosomal glycoproteins called saposins A, B, C, and D [1]
We reported that the two PS receptors show roughly complementary distributions in the rat testis; GPR37L1 is upregulated in germ cells in the earlier stages of spermatogenesis, whereas GPR37 becomes predominant in the later stages [25]
GPR37L1-IR was predominantly observed in the facial nucleus on the operated side (Fig 2I) compared with the untreated side, where almost no GPR37L1-IR was observed (Fig 2H)

Summary

Introduction

Prosaposin (PS) is the precursor protein of four small lysosomal glycoproteins called saposins A, B, C, and D [1]. Increased Prosaposin and its receptors immunoreactivity in the facial nucleus following nerve transection. 13127624; S6 Fig. Original Figures of Fig 4. Https://doi.org/10.6084/ m9.figshare.13127708; S7 Fig. Original Figure of Fig 7.

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