{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:53:58Z","timestamp":1770058438032,"version":"3.49.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08945"],"award-info":[{"award-number":["18K08945"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K07500"],"award-info":[{"award-number":["18K07500"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pone.0241315","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:49:23Z","timestamp":1606855763000},"page":"e0241315","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection"],"prefix":"10.1371","volume":"15","author":[{"given":"Joji","family":"Kunihiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6729-8193","authenticated-orcid":true,"given":"Hiroaki","family":"Nabeka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Wakisaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Unuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Sakirul Islam","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farzana","family":"Islam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Doihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimiko","family":"Yamamiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouichiro","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3159-904X","authenticated-orcid":true,"given":"Seiji","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"issue":"4869","key":"pone.0241315.ref001","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.2842863","article-title":"Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus","volume":"241","author":"JS O'Brien","year":"1988","journal-title":"Science"},{"issue":"3","key":"pone.0241315.ref002","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1096\/fasebj.5.3.2001789","article-title":"Saposin proteins: structure, function, and role in human lysosomal storage disorders","volume":"5","author":"JS O'Brien","year":"1991","journal-title":"FASEB J"},{"issue":"9","key":"pone.0241315.ref003","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0022-2275(20)40540-1","article-title":"Saposins: structure, function, distribution, and molecular genetics","volume":"33","author":"Y Kishimoto","year":"1992","journal-title":"J Lipid Res"},{"issue":"3","key":"pone.0241315.ref004","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/0006-291X(89)92728-9","article-title":"Sphingolipid hydrolase activator proteins and their precursors","volume":"165","author":"A Sano","year":"1989","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"pone.0241315.ref005","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0006-291X(05)80236-0","article-title":"Secretion of sphingolipid hydrolase activator precursor, prosaposin","volume":"176","author":"T Hineno","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0241315.ref006","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1006\/abbi.1993.1328","article-title":"Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins)","volume":"304","author":"M Hiraiwa","year":"1993","journal-title":"Arch Biochem Biophys"},{"issue":"20","key":"pone.0241315.ref007","doi-asserted-by":"crossref","first-page":"9593","DOI":"10.1073\/pnas.91.20.9593","article-title":"Identification of prosaposin as a neurotrophic factor","volume":"91","author":"JS O'Brien","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0241315.ref008","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0165-3806(98)00109-6","article-title":"Prosaposin prevents programmed cell death of rat cerebellar granule neurons in culture","volume":"110","author":"K Tsuboi","year":"1998","journal-title":"Brain Res Dev Brain Res"},{"issue":"5","key":"pone.0241315.ref009","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1046\/j.1471-4159.1996.66052019.x","article-title":"Prosaposin facilitates sciatic nerve regeneration in vivo","volume":"66","author":"Y Kotani","year":"1996","journal-title":"J Neurochem"},{"issue":"2","key":"pone.0241315.ref010","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1006\/bbrc.1994.2558","article-title":"Protection by prosaposin against ischemia-induced learning disability and neuronal loss","volume":"204","author":"A Sano","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"issue":"5","key":"pone.0241315.ref011","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1046\/j.1471-4159.1996.66052197.x","article-title":"A hydrophilic peptide comprising 18 amino acid residues of the prosaposin sequence has neurotrophic activity in vitro and in vivo","volume":"66","author":"Y Kotani","year":"1996","journal-title":"J Neurochem"},{"issue":"5","key":"pone.0241315.ref012","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3109\/00016489.2012.750430","article-title":"Prosaposin-derived peptide alleviates ischaemia-induced hearing loss","volume":"133","author":"T Terashita","year":"2013","journal-title":"Acta Otolaryngol"},{"issue":"5","key":"pone.0241315.ref013","doi-asserted-by":"crossref","first-page":"e0126856","DOI":"10.1371\/journal.pone.0126856","article-title":"A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury","volume":"10","author":"H Nabeka","year":"2015","journal-title":"PLoS One"},{"key":"pone.0241315.ref014","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ibror.2017.07.001","article-title":"Interneurons secrete prosaposin, a neurotrophic factor, to attenuate kainic acid-induced neurotoxicity","volume":"3","author":"H Nabeka","year":"2017","journal-title":"IBRO Reports"},{"key":"pone.0241315.ref015","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ibror.2017.02.002","article-title":"Expression of prosaposin and its receptors in the rat cerebellum after kainic acid injection","volume":"2","author":"X Li","year":"2017","journal-title":"IBRO Rep"},{"issue":"3","key":"pone.0241315.ref016","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.3233\/JAD-160093","article-title":"An 18-mer Peptide Derived from Prosaposin Ameliorates the Effects of A\u03b21\u201342 Neurotoxicity on Hippocampal Neurogenesis and Memory Deficit in Mice","volume":"53","author":"HL Gao","year":"2016","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"pone.0241315.ref017","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/abbi.1997.9958","article-title":"Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid activator proteins): its mechanism and inhibition by ganglioside","volume":"341","author":"M Hiraiwa","year":"1997","journal-title":"Arch Biochem Biophys"},{"issue":"4","key":"pone.0241315.ref018","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/(SICI)1098-1136(199906)26:4<353::AID-GLIA9>3.0.CO;2-G","article-title":"Prosaposin: a myelinotrophic protein that promotes expression of myelin constituents and is secreted after nerve injury","volume":"26","author":"M Hiraiwa","year":"1999","journal-title":"Glia"},{"issue":"23","key":"pone.0241315.ref019","doi-asserted-by":"crossref","first-page":"9529","DOI":"10.1073\/pnas.1219004110","article-title":"GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin","volume":"110","author":"RC Meyer","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pone.0241315.ref020","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0092-8674(01)00407-X","article-title":"An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin","volume":"105","author":"Y Imai","year":"2001","journal-title":"Cell"},{"issue":"41","key":"pone.0241315.ref021","doi-asserted-by":"crossref","first-page":"16486","DOI":"10.1073\/pnas.1314819110","article-title":"Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor","volume":"110","author":"D Marazziti","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0241315.ref022","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/glia.23198","article-title":"G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia","volume":"66","author":"S Jolly","year":"2018","journal-title":"Glia"},{"issue":"11","key":"pone.0241315.ref023","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1002\/glia.23480","article-title":"Glio- and neuro-protection by prosaposin is mediated by orphan G-protein coupled receptors GPR37L1 and GPR37","volume":"66","author":"B Liu","year":"2018","journal-title":"Glia"},{"key":"pone.0241315.ref024","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fphar.2015.00275","article-title":"Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1","volume":"6","author":"NJ Smith","year":"2015","journal-title":"Front Pharmacol"},{"key":"pone.0241315.ref025","unstructured":"Yamamiya K, Li X, Nabeka H, imokawa T, Khan MSI, Doihara T, et al. Function of prosaposin in the testis. The 124th Annual Meeting of the Japanese Association of Anatomists2019. p. P176."},{"issue":"3","key":"pone.0241315.ref026","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.neures.2005.03.009","article-title":"Changes in expression of prosaposin in the rat facial nerve nucleus after facial nerve transection","volume":"52","author":"K Unuma","year":"2005","journal-title":"Neuroscience research"},{"issue":"1","key":"pone.0241315.ref027","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neures.2007.09.010","article-title":"Expression patterns in alternative splicing forms of prosaposin mRNA in the rat facial nerve nucleus after facial nerve transection","volume":"60","author":"J Chen","year":"2008","journal-title":"Neuroscience research"},{"issue":"3","key":"pone.0241315.ref028","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00441-013-1575-0","article-title":"Distribution of prosaposin in rat lymphatic tissues","volume":"352","author":"T Shimokawa","year":"2013","journal-title":"Cell and tissue research"},{"issue":"11","key":"pone.0241315.ref029","doi-asserted-by":"crossref","first-page":"e80032","DOI":"10.1371\/journal.pone.0080032","article-title":"Decrease in prosaposin in the Dystrophic mdx mouse brain","volume":"8","author":"HL Gao","year":"2013","journal-title":"PLoS One"},{"issue":"12","key":"pone.0241315.ref030","doi-asserted-by":"crossref","first-page":"e110534","DOI":"10.1371\/journal.pone.0110534","article-title":"Prosaposin Overexpression following Kainic Acid-Induced Neurotoxicity","volume":"9","author":"H Nabeka","year":"2014","journal-title":"PLOS ONE"},{"issue":"12","key":"pone.0241315.ref031","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1021\/bi00386a008","article-title":"Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells","volume":"26","author":"MW Collard","year":"1987","journal-title":"Biochemistry"},{"issue":"12","key":"pone.0241315.ref032","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1021\/bi00412a050","article-title":"Biosynthesis and molecular cloning of sulfated glycoprotein 1 secreted by rat Sertoli cells: sequence similarity with the 70-kilodalton precursor to sulfatide\/GM1 activator","volume":"27","author":"MW Collard","year":"1988","journal-title":"Biochemistry"},{"issue":"3","key":"pone.0241315.ref033","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/jnc.12741","article-title":"The protein interacting with C-kinase (PICK1) interacts with and attenuates parkin-associated endothelial-like (PAEL) receptor-mediated cell death","volume":"130","author":"P Dutta","year":"2014","journal-title":"J Neurochem"},{"issue":"1","key":"pone.0241315.ref034","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0169-328X(99)00092-3","article-title":"Molecular cloning and characterization of two putative G protein-coupled receptors which are highly expressed in the central nervous system","volume":"69","author":"N Leng","year":"1999","journal-title":"Brain Res Mol Brain Res"},{"key":"pone.0241315.ref035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2014.08.022","article-title":"The protective role of prosaposin and its receptors in the nervous system","volume":"1585","author":"RC Meyer","year":"2014","journal-title":"Brain Res"},{"issue":"43","key":"pone.0241315.ref036","doi-asserted-by":"crossref","first-page":"10286","DOI":"10.1021\/bi9013775","article-title":"GPR37 surface expression enhancement via N-terminal truncation or protein-protein interactions","volume":"48","author":"JH Dunham","year":"2009","journal-title":"Biochemistry"},{"issue":"2","key":"pone.0241315.ref037","first-page":"237","article-title":"Prosaptide prevents paclitaxel neurotoxicity","volume":"19","author":"WM Campana","year":"1998","journal-title":"Neurotoxicology"},{"key":"pone.0241315.ref038","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.brainres.2018.12.027","article-title":"Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage","volume":"1710","author":"K Sekiya","year":"2019","journal-title":"Brain Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0241315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T03:20:04Z","timestamp":1618543204000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0241315"}},"subtitle":[],"editor":[{"given":"Faramarz","family":"Dehghani","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0241315","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]}}}