Discrete roles for secreted and transmembrane semaphorins in neuronal growth cone guidance in vivo.
(1/443)
From the initial stages of axon outgrowth to the formation of a functioning synapse, neuronal growth cones continuously integrate and respond to multiple guidance cues. To investigate the role of semaphorins in the establishment of appropriate axon trajectories, we have characterized a novel secreted semaphorin in grasshopper, gSema 2a. Sema 2a is expressed in a gradient in the developing limb bud epithelium during Ti pioneer axon outgrowth. We demonstrate that Sema 2a acts as chemorepulsive guidance molecule critical for axon fasciculation and for determining both the initial direction and subsequent pathfinding events of the Ti axon projection. Interestingly, simultaneous perturbation of both secreted Sema 2a and transmembrane Sema I results in a broader range and increased incidence of abnormal Ti pioneer axon phenotypes, indicating that different semaphorin family members can provide functionally distinct guidance information to the same growth cone in vivo. (+info)
Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108.
(2/443)
CDw108, also known as the John-Milton-Hagen human blood group Ag, is an 80-kDa glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is preferentially expressed on activated lymphocytes and E. The molecular characteristics and biological function of the CDw108 were not clarified previously. In this manuscript, we identify the cDNA clone containing the entire coding sequence of the CDw108 gene and report its molecular characteristics. The 1998-base pairs of the open reading frame of the cloned cDNA encoded a protein of 666 amino acids (aa), including the 46 aa of the signal peptide and the 19 aa of the GPI-anchor motif. Thus, the membrane-anchoring form of CDw108 was the 602 aa, and the estimated molecular mass of the unglycosylated form was 68 kDa. The RGD (Arg-Gly-Asp) cell attachment sequence and the five potential N-linked glycosylation sites were located on the membrane-anchoring form. Flow cytometric and immunoprecipitation analyses of the CDw108 cDNA transfectants confirmed that the cloned cDNA encoded the native form of CDw108. The CDw108 mRNA was expressed in activated PBMCs as well as in the spleen, thymus, testis, placenta, and brain, but was not expressed in any other tissues tested. Radiation hybrid mapping indicated that the CDw108 gene was located in the middle of the long arm of chromosome 15 (15q23-24). This molecular information will be critical for understanding the biological function of the CDw108 Ag. (+info)
Neural development: The semantics of axon guidance.
(3/443)
Recent studies of the semaphorin family of axon guidance signals and their receptors have revealed a surprising versatility in the ways that they can be used solve problems in neural development, and provided new opportunities for understanding how guidance information is interpreted beneath the cell surface. (+info)
A PDZ protein regulates the distribution of the transmembrane semaphorin, M-SemF.
(4/443)
M-SemF is a membrane-associated, neurally enriched member of the semaphorin family of axon guidance signals. We considered whether the cytoplasmic domain of M-SemF might possess a signaling function and/or might control the distribution of M-SemF on the cell surface. We identify a PDZ-containing neural protein as an M-SemF cytoplasmic domain-associated protein (SEMCAP-1). SEMCAP-2 is a closely related nonneuronal protein. SEMCAP-1 has recently also been identified as GIPC, by virtue of its interaction with the RGS protein GAIP in vitro (De Vries, L., Lou, X., Zhao, G., Zheng, B., and Farquhar, M. G. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12340-12345). Expression studies support the notion that SEMCAP-1(GIPC) interacts with M-SemF, but not GAIP, in brain. Lung SEMCAP-2 and SEMCAP-1(GIPC) are potential partners for both GAIP and M-SemF. The protein interaction requires the single PDZ domain of SEMCAP-1(GIPC) and the carboxyl-terminal four residues of M-SemF, ESSV. While SEMCAP-1(GIPC) also interacts with SemC, it does not interact with other proteins containing a class I PDZ binding motif, nor does M-SemF interact with other class I PDZ proteins. Co-expression of SEMCAP-1(GIPC) induces the redistribution of dispersed M-SemF into detergent-resistant aggregates in HEK293 cells. Thus, SEMCAP-1(GIPC) appears to regulate the subcellular distribution of M-SemF in brain, and SEMCAPs could link M-SemF to G protein signal transduction pathways. (+info)
Characterization and expression of sema4g, a novel member of the semaphorin gene family.
(5/443)
Semaphorins constitute a large and growing gene family, several members of which are axon guidance molecules. We report the characterization of sema4g, a novel class IV member of the semaphorin gene family, located on mouse chromosome 19. sema4g is expressed early in development in the brain, spinal cord, and several sensory organs as well as specific populations of projection neurons, compatible with the well-established function of semaphorins as axon guidance molecules. (+info)
Switch in the protein tyrosine phosphatase associated with human CD100 semaphorin at terminal B-cell differentiation stage.
(6/443)
Human CD100, the first semaphorin identified in the immune system, is a transmembrane protein involved in T-cell activation. In the present study, we showed that activation of peripheral blood or tonsillar B lymphocytes induced the expression of CD100 in CD38(+)CD138(-) cell populations, including in CD148(+) subpopulations, thus expressing a memory B-cell-like phenotype. Using an in vitro enzymatic assay, we found that protein tyrosine phosphatase (PTP) activities were immunoprecipitated with CD100 in these cell populations, which were isolated by cell sorting, as well as in most B-cell lines representing various stages of B-cell differentiation. Immunodepletion and Western blotting experiments demonstrated that CD45 was the PTP associated with CD100 in cell lines displaying pre-B, activated B, and pre-plasma cell phenotypes. CD45 also accounted for PTP activity immunoprecipitated with CD100 in CD38(+)CD138(-) cells sorted after activation of peripheral blood or tonsillar B lymphocytes. In contrast, no CD100-CD45 association was observed in plasma cell lines corresponding to the terminal B-cell differentiation stage. CD148, the other transmembrane PTP known to be implicated in lymphocyte signaling pathways, was either only partly involved in the CD100-associated PTP activity or not expressed in plasma cell lines, indicating the association of CD100 with another main PTP. Our data show that CD100 is differentially expressed and can functionally associate with distinct PTPs in B cells depending on their activation and maturation state. They also provide evidence for a switch in the CD100-associated PTP at terminal stage of B-cell differentiation. (+info)
Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis.
(7/443)
We report the sequence and expression analysis of two new Drosophila members of the Semaphorin family. Both proteins show the presence of Semaphorin domains and transmembrane domains. Both genes are expressed maternally and in embryos, and reveal distinct expression patterns much earlier than the onset of neurogenesis. We also present an overview of the domain structure of all so far known semaphorins in Drosophila. Furthermore, we compared all Drosophila and C. elegans Semaphorins and discuss them in the light of their evolution. (+info)
Iron overload and gene expression in HepG2 cells: analysis by differential display.
(8/443)
The aim of the present study was to evaluate the effect of iron overload on gene expression in HepG2 cells by differential display. Iron-treated cells showed a 50% decrease in apolipoprotein B100 (Apo B100) and a 2- and 3-fold increase in semaphorin cd100 and aldose reductase mRNA, respectively, with parallel variations in Apo B100 and aldose reductase proteins. These effects were time-dependent. Vitamin E prevented the increase in aldose reductase expression, but had no effect on Apo B100 and semaphorin cd100. Treatment with hydrogen peroxide and 4-hydroxy-2,3-nonenal increased only aldose reductase mRNA. These data suggest that iron can affect mRNA levels by lipid peroxidation-dependent and -independent pathways. (+info)