Prosaposin: threshold rescue and analysis of the “neuritogenic” region in transgenic mice

Sun, Ying; Qi, Xiaoyang; Witte, David P.; Ponce, Elvira; Kondoh, Keiji; Quinn, Brian; Grabowski, Gregory A.

doi:10.1016/s1096-7192(02)00114-2

Cited by 30 publications

(55 citation statements)

References 31 publications

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“…This current study characterizes prosaposin within the rat cochlea and reports on the anatomical and functional results in the organ of Corti when prosaposin function is abolished in a knockout (KO) mouse (Sun et al, 2002). Together, the findings in this study have implications for our understanding of the development and maintenance of hearing.…”

Section: Introductionmentioning

confidence: 82%

“…Prosaposin knock-out mice (generously provided by Dr. Greg Grabowski) (Sun et al, 2002) ranging from P12 to P30 were anesthetized and their cochleae were isolated, dissected, perfused through the round window with both 2% paraformaldehyde and 2% glutaraldehyde in 0.1 M phosphate buffer, pH 7.4, and then incubated in the same fixative overnight at 4°C. The cochleae were rinsed with 0.1 M PB and post fixed in 1% osmium tetroxide for 1 h. The bone surrounding the cochlea was thinned and the cochlea subsequently immersed in 5% EDTA (0.2 M).…”

Section: Knock-out Mouse Histopathologymentioning

confidence: 99%

“…To gain some insight into the possible functional role of prosaposin or saposins A-D within the organ of Corti, prosaposin knock-out mice were studied (Sun et al, 2002). It has previously been demonstrated that both prosaposin and one of its mature, cleaved proteins, saposin C, can cause neuronal outgrowth in cell cultures (O'Brien et al, 1995).…”

Section: Prosaposin Knock-out Mice Studiesmentioning

confidence: 99%

“…It has previously been demonstrated that both prosaposin and one of its mature, cleaved proteins, saposin C, can cause neuronal outgrowth in cell cultures (O'Brien et al, 1995). The CNS effects of such a mutation have already been described (Sun et al, 2002), however the effects on the auditory pathway and end organ have not been reported. Because the homozygote (Ϫ/Ϫ) KO mice uniformly expire shortly after P30, all studies were performed before this time.…”

Section: Prosaposin Knock-out Mice Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Akil¹,

Chang²,

Hiel³

et al. 2006

J. Neurosci.

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Section: Introductionmentioning

confidence: 82%

Section: Knock-out Mouse Histopathologymentioning

confidence: 99%

Section: Prosaposin Knock-out Mice Studiesmentioning

confidence: 99%

Section: Prosaposin Knock-out Mice Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Akil¹,

Chang²,

Hiel³

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

“…The phenotype of mice expressing reduced levels of prosaposin lends support to this notion. Thus, a ϳ60% reduced prosaposin mRNA level causes accumulation and intralysosomal deposition of sulfatide in the brain stem and kidney of mice (39). Moreover, changes of the lipid pattern are detectable in mice which are heterozygous for a disrupted prosaposin allele (40).…”

Section: Discussionmentioning

confidence: 99%

Saposin B-dependent Reconstitution of Arylsulfatase A Activity in Vitro and in Cell Culture Models of Metachromatic Leukodystrophy

Matzner

Breiden

Schwarzmann

et al. 2009

Journal of Biological Chemistry

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Glio‐ and neuro‐protection by prosaposin is mediated by orphan G‐protein coupled receptors GPR37L1 and GPR37

Liu

Mosienko

Cardoso

et al. 2018

Glia

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Discovery of neuroprotective pathways is one of the major priorities for neuroscience. Astrocytes are natural neuroprotectors and it is likely that brain resilience can be enhanced by mobilizing their protective potential. Among G‐protein coupled receptors expressed by astrocytes, two highly related receptors, GPR37L1 and GPR37, are of particular interest. Previous studies suggested that these receptors are activated by a peptide Saposin C and its neuroactive fragments (prosaptide TX14(A)), which were demonstrated to be neuroprotective in various animal models by several groups. However, pairing of Saposin C or prosaptides with GPR37L1/GPR37 has been challenged and presently GPR37L1/GPR37 have regained their orphan status. Here, we demonstrate that in their natural habitat, astrocytes, these receptors mediate a range of effects of TX14(A), including protection from oxidative stress. The Saposin C/GPR37L1/GPR37 pathway is also involved in the neuroprotective effect of astrocytes on neurons subjected to oxidative stress. The action of TX14(A) is at least partially mediated by Gi‐proteins and the cAMP‐PKA axis. On the other hand, when recombinant GPR37L1 or GPR37 are expressed in HEK293 cells, they are not functional and do not respond to TX14(A), which explains unsuccessful attempts to confirm the ligand‐receptor pairing. Therefore, this study identifies GPR37L1/GPR37 as the receptors for TX14(A), and, by extension of Saposin C, and paves the way for the development of neuroprotective therapeutics acting via these receptors. A video abstract of this article can be found at: https://www.youtube.com/watch?v=qTn13My9Sz8

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Prosaposin: threshold rescue and analysis of the “neuritogenic” region in transgenic mice

Cited by 30 publications

References 31 publications

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin

Saposin B-dependent Reconstitution of Arylsulfatase A Activity in Vitro and in Cell Culture Models of Metachromatic Leukodystrophy

Glio‐ and neuro‐protection by prosaposin is mediated by orphan G‐protein coupled receptors GPR37L1 and GPR37

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