Biomedical subjects

Kyle J Roux

Publications and source records attributed to Kyle J Roux.

4 recordsLinked to original sources

PubMed2006

Nuclear envelope defects in muscular dystrophy.

Muscular dystrophies are a heterogeneous group of disorders linked to defects in 20-30 different genes. Mutations in the genes encoding a pair of nuclear envelope proteins, emerin and lamin A/C, have been shown to cause the X-linked and autosomal forms respectively of Emery-Dreifuss muscular dystrophy. A third form of muscular dystrophy, limb girdle muscular dystrophy 1b, has also been linked to mutations in the lamin A/C gene. Given that these two genes are ubiquitously expressed, a major goal is to determine how they can be associated with tissue specific diseases. Recent results suggest that lamin A/C and emerin contribute to the maintenance of nuclear envelope structure and at the same time may modulate the expression patterns of certain mechanosensitive and stress induced genes. Both emerin and lamin A/C may play an important role in the response of cells to mechanical stress and in this way may help to maintain muscle cell integrity.

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PubMed2006

From pore to kinetochore and back: regulating envelope assembly.

Reassembly of the nuclear envelope following mitosis is a fundamental process that remains only partially understood. Two recent reports by and in the September 5 issue of Current Biology identify a novel protein, MEL-28, that shuttles between the nuclear pore complex and kinetochore and is essential for envelope assembly in C. elegans early embryos.

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PubMed2005

Modulation of epithelial morphology, monolayer permeability, and cell migration by growth arrest specific 3/peripheral myelin protein 22.

Peripheral myelin protein 22 (PMP22) is associated with a subset of hereditary peripheral neuropathies. Although predominantly recognized as a transmembrane constituent of peripheral nerve myelin, PMP22 is localized to epithelial and endothelial cell-cell junctions, where its function remains unknown. In this report, we investigated the role of PMP22 in epithelial biology. Expression of human PMP22 (hPMP22) slows cell growth and induces a flattened morphology in Madin-Darby canine kidney (MDCK) cells. The transepithelial electrical resistance (TER) and paracellular flux of MDCK monolayers are elevated by hPMP22 expression. After calcium switch, peptides corresponding to the second, but not the first, extracellular loop of PMP22 perturb the recovery of TER and paracellular flux. Finally, subsequent to wounding, epithelial monolayers expressing hPMP22 fail to migrate normally. These results indicate that PMP22 is capable of modulating several aspects of epithelial cell biology, including junctional permeability and wound closure.

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PubMed2004

The temporospatial expression of peripheral myelin protein 22 at the developing blood-nerve and blood-brain barriers.

Peripheral myelin protein 22 (PMP22), also known as growth arrest-specific gene 3 (gas3), is a tetraspan membrane protein whose misexpression is associated with demyelinating peripheral neuropathies. Although the function of PMP22 in Schwann cells is unknown, the protein is found at intercellular junctions of various epithelia and endothelia. To begin to elucidate the role of PMP22 at cell junctions, we examined the temporal expression and protein localization during development and maturation of the rat blood-nerve barrier (BNB) and blood-brain barrier (BBB). Developing and adult rat sciatic nerves and brains were coimmunostained for PMP22 and known junctional proteins including zonula occludens-1 (ZO-1), occludin, and claudin-5. Prior to the maturation of the BNB and BBB and detection of the tight junction protein occludin, PMP22 is present at ZO-1 positive endothelial junctions of the sciatic nerve and brain cortex. The subcellular localization of PMP22 in cultured brain endothelia was confirmed by internalization with ZO-1 after EGTA-induced disruption of cell junctions. In choroid epithelia, PMP22 is detected along with occludin and ZO-1 as early as embryonic day 15 (E15). In agreement, PMP22 message is elevated in P1 rat brain microvasculature and choroid epithelia, compared with total cortex. Additionally, neuroepithelial cell junctions in the embryonic rat brain are immunoreactive for PMP22, ZO-1, and beta-catenin but not occludin. Together, these studies identify PMP22 as an early constituent of intercellular junctions in the developing and mature rat BNB and BBB.

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