Biomedical subjects

Irma Machuca-Gayet

Publications and source records attributed to Irma Machuca-Gayet.

4 recordsLinked to original sources

PubMed2005

A role for the neuronal protein collapsin response mediator protein 2 in T lymphocyte polarization and migration.

The semaphorin-signaling transducer collapsin response mediator protein 2 (CRMP2) has been identified in the nervous system where it mediates Sema3A-induced growth cone navigation. In the present study, we provide first evidence that CRMP2 is present in the immune system and plays a critical role in T lymphocyte function. CRMP2 redistribution at the uropod in polarized T cells, a structural support of lymphocyte motility, suggests that it may regulate T cell migration. This was evidenced in primary T cells by small-interfering RNA-mediated CRMP2 gene silencing and blocking Ab, as well as CRMP2 overexpression in Jurkat T cells tested in a chemokine- and semaphorin-mediated transmigration assay. Expression analysis in PBMC from healthy donors showed that CRMP2 is enhanced in cell subsets bearing the activation markers CD69+ and HLA-DR+. Heightened expression in T lymphocytes of patients suffering from neuroinflammatory disease with enhanced T cell-transmigrating activity points to a role for CRMP2 in pathogenesis. The elucidation of the signals and mechanisms that control this pathway will lead to a better understanding of T cell trafficking in physiological and pathological situations.

Antigens, CD↗

PubMed2005

Odontoblast expression of semaphorin 7A during innervation of human dentin.

Semaphorin 7A (SEMA 7A) is a membrane-anchored member of the semaphorin family of guidance proteins, previously identified in the immune system. Expressed in central and peripheral nervous system during embryonic and post-natal stages, it can mediate neuronal functions by promoting axonal growth. We show here that SEMA 7A is expressed in human odontoblasts in vivo and in vitro and that its expression is correlated with the establishment of dentin-pulp complex terminal innervation . Co-cultures of trigeminal ganglion (TG) with COS cells overexpressing SEMA 7A demonstrate that SEMA 7A can promote the growth of trigeminal nerve fibers. Finally, by RT-PCR and immunochemistry, we show that beta1-integrin, a SEMA 7A putative receptor, is expressed in pulpal nerve fibers but we failed to detect a co-localization between nerves and odontoblasts through these molecules. On the basis of these data, we suggest that SEMA 7A might be a molecule involved in the terminal innervation of the dentin-pulp complex.

Adolescent↗

PubMed2005

Expression and function of semaphorin 7A in bone cells.

BACKGROUND INFORMATION: Sema-7A is a glycosylphosphatidylinositol-anchored semaphorin that was first identified in the immune system. It is a member of a large family of proteins involved in axon guidance signalling. Sema-7A is expressed in the myeloid and the lymphoid lineage and seems to be involved in cytokine expression and chemotaxy through its receptor Plexin C1. However, it can promote axon outgrowth, acting through a beta1 subunit-containing integrin receptor. RESULTS AND CONCLUSIONS: In the present study, we have investigated its regulation and function in bone cells. Semiquantitative reverse transcriptase-PCR demonstrated that Sema-7A mRNA is present during all stages of osteoblast differentiation and maturation in mouse calvaria cells and in MC3T3 cell line in vitro. Its expression is also regulated during primary osteoclast differentiation in vitro. We report that Sema-7A is capable of increasing the migration of MC3T3 cells and that this process is mediated by the mitogen-activated protein kinase pathway in osteoblasts, probably through the integrin subunit beta1. Moreover, the addition of recombinant soluble Sema-7A to the culture enhances osteoclast fusion. These findings indicate for the first time the possible involvement of Sema-7A in bone cell differentiation.

Animals↗

PubMed2002

Transcriptional activity of nuclei in multinucleated osteoclasts and its modulation by calcitonin.

The function of osteoclasts is to digest the calcified bone matrix. Osteoclasts, together with myotubes, are among the rare examples of multinucleated cells found in higher vertebrates, resulting from the fusion of mononucleated progenitors belonging to the monocyte/macrophage lineage. So far, no information is available about function and transcriptional activity of multiple nuclei in osteoclasts. We have used a run-on technique to visualize RNA synthesis in individual nucleus. We provide the first evidence that nuclei of resorbing osteoclasts, isolated from chick embryo long bones, or differentiated in vitro from murine spleen cells in presence of RANKL and macrophage-colony stimulating factor, are all transcriptionally active. Nevertheless, if transcriptional activity is the same for all the nuclei within a cell, its level varies between osteoclasts: osteoclasts with highly active nuclei are always associated with resorption pits. We found that global transcription activity of resorbing osteoclasts seeded on calcified matrix is down-regulated after 5-h treatment with calcitonin, which transiently blocks resorption. This effect is reversible because calcitonin removal led to nuclear transcription activation. These results indicate a strong correlation between transcription and resorption. Finally, our data indicate that the resorption pit surface is linearly related to the nuclei number per osteoclast, strongly suggesting that functional advantage of osteoclast multinucleation is to improve resorption efficiency.

Animals↗