Functional Organization of Saposin C

Qi, Xiaoyang; Qin, Wen; Sun, Ying; Kondoh, Keiji; Grabowski, Gregory A.

doi:10.1074/jbc.271.12.6874

Cited by 70 publications

(52 citation statements)

References 37 publications

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“…Although the increased content of sulfatide after treatment could also be due to decreased degradation, the demonstration of increase sulfate incorporation into sulfatide, the rate and magnitude of the sulfatide increase, and phosphorylation of MAPK indicate enhanced synthesis as the basis for the increase. Prosaposin and prosaptides appear to induce both differentiation of neuronal cells (2,3,8) and synthesis of gangliosides (19); the present study indicates that Schwann cells and oligodendrocytes respond similarly. Studies are underway in experimental animals to determine the efficacy of prosaptides as therapeutic agents for the treatment of demyelinating peripheral neuropathy and to ascertain their effects upon myelin synthesis in central demyelinating models.…”

Section: Discussionsupporting

confidence: 58%

“…We have described (3) several synthetic peptides derived from this region that are as biologically active as prosaposin; we named these peptides ''prosaptides.'' Prosaposin and prosaptides are active on a variety of neuronal cells including hippocampal neurons (5,6), spinal cord ␣-motor neurons (7), sensory neurons of the dorsal root ganglion (7), cerebellar granule cell neurons (3), and neuroblastoma cells (2)(3)(4)8). In each of these cells, prosaposin or prosaptides stimulate neurite outgrowth in nanomolar concentrations and prevent cell death.…”

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confidence: 99%

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Cell death prevention, mitogen-activated protein kinase stimulation, and increased sulfatide concentrations in Schwann cells and oligodendrocytes by prosaposin and prosaptides

Hiraiwa

Taylor

Campana

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Prosaposin, the precursor of saposins A, B, C, and D, was recently identified as a neurotrophic factor. Herein prosaposin was found to increase sulfatide concentrations in primary and transformed Schwann cells (iSC) and oligodendrocytes (differentiated CG4 cells). Of the four mature saposins, only saposin C was found to increase sulfatide concentrations in these cell types. A similar result was obtained by using peptides (

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

Cell death prevention, mitogen-activated protein kinase stimulation, and increased sulfatide concentrations in Schwann cells and oligodendrocytes by prosaposin and prosaptides

Hiraiwa

Taylor

Campana

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…In PC12 and neuroblastoma cell lines, prosaposin and SAP-C have been shown to induce neurite outgrowth and act as neurotrophic factors (30). The neurotrophic activity in the molecules was localized to a stretch of around 10 amino acids (30,31). Interestingly, MSAP lacks this stretch of amino acids.…”

Section: Discussionmentioning

confidence: 99%

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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Interactions between the cell membrane and the cytoskeleton play a major role in different aspects of cell differentiation, such as cell motility, cell division, and establishment of cellular architecture. Of particular importance in this context is the association of cortical actin with the cell membrane. The ERM 1 proteins, ezrin, radixin, and moesin, are members of the large 4.1 protein family and are involved in membrane-cytoskeleton interactions. They link the actin cytoskeleton to membranebound proteins located at different membrane sites, i.e. microvilli, membrane ruffles, and cell-cell contacts (1-3). This is accomplished by binding of the C-terminal part of the ERM proteins to actin and of the N-terminal FERM domain to specific membrane proteins (4). FERM domains have been found in many different proteins and are thought to be modules for protein-protein and protein-membrane interactions (5). The ERM proteins are involved in cell adhesion and signal transduction events through phosphorylation (6, 7) and interaction with phosphoinositides (8). The ERM proteins play an important role in the activation of Rho family proteins and can interact both downstream (9) and upstream (10) of Rho.In addition, the ERM proteins are involved in membrane dynamics (11). When ezrin, radixin, and moesin were simultaneously inactivated by antisense treatment in epithelial cells, cell-cell and cell-substratum adhesion was altered (12). Double suppression of radixin and moesin, but not ezrin and radixin or moesin, alters growth cone motility, inhibiting neurite extension (13). In contrast, overexpression of ezrin in insect cells leads to enhanced cell adhesion (14). The mechanisms behind these effects are, however, not well understood, but ERM proteins are known to interact with various proteins such as CD44 and ICAM-1, -2, and -3, which helps in establishing membrane specializations (for review, see Ref. 7). The identification and characterization of further binding partners for ERM proteins can give new insights into the function of these proteins.We have recently identified a novel ERM family protein, MIR, which has an ERM domain at the N terminus and lacks actin binding, instead possessing a RING domain in the Cterminal region (15). Overexpression of MIR abrogated neurite outgrowth in PC12 cells, an effect that may be brought about by its interaction with the myosin regulatory light chain (MRLC). We describe here a novel protein interacting with MIR, called MIR-interacting saposin-like protein (MSAP), which stimulates neurite outgrowth. Sequence comparisons showed that MSAP contains a saposin domain, which is found, among others, in the sphingolipid activator proteins, the saposins (16), and in some saposin-like proteins with a similar structure (17). The effects of MSAP on neurite outgrowth were reduced by MIR. MIR was shown to induce a decrease in the levels of MRLC, which could be blocked by overexpression of MSAP or by inhibition of proteasome activity. Evidence was obtained that the decrease in MRLC levels by MIR invo...

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“…Prosaposin is unique among putative "lysosomal proteins" since it has housekeeping functions (43) and growth-promoting effects (32)(33)(34). Only the protector protein may have similar intra-and extracellular functions (44,45).…”

Section: Discussionmentioning

confidence: 99%

“…Although the precise physiological function of intact prosaposin has not been defined, it functions in vitro as a glycosphingolipid transfer protein (31,32) and ex vivo as a neurotrophic agent (32,33). Administration of prosaposin to culture media of neuronal cells or in fluid surrounding injured sural nerves leads to neurite outgrowth (32,33) or regeneration (34), respectively.…”

mentioning

confidence: 99%