Saposin-C from bovine spleen; complete amino acid sequence and relation between the structure and its biological activity

Sano, Akira; Mizuno, Tatsuo; Kondoh, Keiji; Hineno, Takashi; Ueno, Shu‐ichi; Kakimoto, Yasuo; Morita, Naoki

doi:10.1016/0167-4838(92)90426-e

Cited by 22 publications

(14 citation statements)

References 20 publications

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“…The pattern of prosaposin processing in mammals varies from tissue to tissue. Using immunoblot analysis, saposins have been shown to dominate in the spleen, lung, liver, and kidney, whereas the precursor form (prosaposin) appears to be produced mainly in the brain and muscle (Sano et al 1988(Sano et al , 1989(Sano et al , 1992Kishimoto et al 1992). We demonstrated that prosaposin, which does not greatly contribute to the hydrolysis of sphingolipids, is abundant in various secretory fluids, especially cerebrospinal fluid, and that it is secreted from the lysosome-like granules of platelets on stimulation by thrombin .…”

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Distribution of prosaposin in the rat nervous system

et al. 2007

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Prosaposin is the precursor of four sphingolipid activator proteins (saposins A, B, C, and D) for lysosomal hydrolases and is abundant in the nervous system and muscle. In addition to its role as a precursor of saposins in lysosomes, intact prosaposin has neurotrophic effects in vivo or in vitro when supplied exogenously. We examined the distribution of prosaposin in the central and peripheral nervous systems and its intracellular distribution. Using a monospecific antisaposin D antibody that crossreacts with prosaposin but not with saposins A, B, or C, immunoblot experiments showed that both the central and peripheral nervous systems express unprocessed prosaposin and little saposin D. Using the antisaposin D antibodies, we demonstrated that prosaposin is abundant in almost all neurons of both the central and peripheral nervous systems, including autonomic nerves, as well as motor and sensory nerves. Immunoelectron microscopy using double staining with antisaposin D and anticathepsin D antibodies showed strong prosaposin immunoreactivity mainly in the lysosomal granules in the neurons in both the central and peripheral nervous systems. The expression of prosaposin mRNA, examined using in situ hybridization, was observed in these same neurons. Our results suggest that prosaposin is synthesized ubiquitously in neurons of both the central and peripheral nervous systems.

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Distribution of prosaposin in the rat nervous system

et al. 2007

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“…Proteolytic cleavage of the mature prosaposin glycoprotein within the lysosome produces the mature saposins (21,22). Saposins B, C, and D contain single occupied N-glycosylation sites, and saposin A contains two (23)(24)(25)(26)(27).…”

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Proteolytic Processing Patterns of Prosaposin in Insect and Mammalian Cells

Leonova

Bencosme

et al. 1996

Journal of Biological Chemistry

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“…The SOFT-SEC (Softwood Co.) program was used to convert data files (ASCII files) from the JASCO spectrophotometer for use FIGURE 2: Amino acid sequences of saposins A and C and the amino acid sequence of the neuritogenic region. Human, bovine, and guinea pig saposin C amino acid sequences were from the chemically determined amino acid sequence (43)(44)(45). Mouse and rat amino acid sequences were deduced from cDNA sequences.…”

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Conformational and Amino Acid Residue Requirements for the Saposin C Neuritogenic Effect

Kondoh

Krusling

et al. 1999

Biochemistry

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Prosaposin is the precursor of four activator proteins, termed saposins A, B, C, and D, that are required for much of glycosphingolipid hydrolysis. The intact precursor also has neurite outgrowth activity ex vivo and in vivo that is localized to amino acid residues 22-31 of saposin C. Across species, this saposin C region has a high degree of identity and similarity with amino acids in the analogous region of saposin A. Wild-type and mutant saposins C and A from human and mouse were expressed in E. coli. Pure proteins, synthetic peptide analogues, conformation-specific antibodies, and CD spectroscopy were used to evaluate the basis of the ex vivo neuritogenic effect. Wild-type saposin A had no neuritogenic activity whereas reduced and alkylated saposin A did. Introduction of the conserved saposin A Tyr 30 (Y30) into saposin C at the analogous position 31, a conserved Ala(A)/Gly(G)31, diminished neuritogenic activity by 50-60%. Nondenatured saposin A with an introduced A30 acquired substantial neuritogenic activity. Polyclonal antibodies directed against the NH2-terminus of saposin C cross-reacted well with reduced and alkylated saposins C and A, wild-type saposin C, and saposin A [Y30A], poorly with saposin C [A31Y], and not at all with wild-type saposin A. CD spectra of wild-type and mutant saposins C and A, the corresponding neuritogenic region of saposin C, and the analogous region of saposin A showed that more "saposin C-like" molecules had neuritogenic properties. Those with more "saposin A-like" spectra did not. These studies show that the neuritogenic activity of saposin C requires specific placement of amino acids, and that Y30 of saposin A significantly alters local conformation in this critical region and suppresses neuritogenic activity.

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Saposin-C from bovine spleen; complete amino acid sequence and relation between the structure and its biological activity

Cited by 22 publications

References 20 publications

Distribution of prosaposin in the rat nervous system

Distribution of prosaposin in the rat nervous system

Proteolytic Processing Patterns of Prosaposin in Insect and Mammalian Cells

Conformational and Amino Acid Residue Requirements for the Saposin C Neuritogenic Effect

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