PubMed Health⌕ Search

Biomedical subjects

M Pendergast

Publications and source records attributed to M Pendergast.

10 recordsLinked to original sources
PubMed1999

Touching the problem.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway.

Cell-cell interactions mediated via cell adhesion molecules (CAMs) are dynamically regulated during nervous system development. One mechanism to control the amount of cell surface CAMs is to regulate their recycling from the plasma membrane. The L1 subfamily of CAMs has a highly conserved cytoplasmic domain that contains a tyrosine, followed by the alternatively spliced RSLE (Arg-Ser-Leu-Glu) sequence. The resulting sequence of YRSL conforms to a tyrosine-based sorting signal that mediates clathrin-dependent endocytosis of signal-bearing proteins. The present study shows that L1 associates in rat brain with AP-2, a clathrin adaptor that captures plasma membrane proteins with tyrosine-based signals for endocytosis by coated pits. In vitro assays demonstrate that this interaction occurs via the YRSL sequence of L1 and the mu 2 chain of AP-2. In L1-transfected 3T3 cells, L1 endocytosis is blocked by dominant-negative dynamin that specifically disrupts clathrin-mediated internalization. Furthermore, endocytosed L1 colocalizes with the transferrin receptor (TfR), a marker for clathrin-mediated internalization. Mutant forms of L1 that lack the YRSL do not colocalize with TfR, indicating that the YRSL mediates endocytosis of L1. In neurons, L1 is endocytosed preferentially at the rear of axonal growth cones, colocalizing with Eps15, another marker for the clathrin endocytic pathway. These results establish a mechanism by which L1 can be internalized from the cell surface and suggest that an active region of L1 endocytosis at the rear of growth cones is important in L1-dependent axon growth.

3T3 Cells↗
PubMed1997

The role of cell adhesion molecule L1 in axonal extension, growth cone motility, and signal transduction.

Axonal pathfinding is a complex process dependent on cell-cell and cell-matrix interactions. L1 is a cell adhesion molecule that is abundant in the nervous system and that is concentrated on axons. As a culture substrate, L1 is a potent promoter of neurite outgrowth and elicits specific growth cone behavior. It interacts with the actin cytoskeleton via an ankyrin linkage and promotes specific distribution of F-actin within the growth cone. In addition, L1 has been implicated in signal transduction. For example, L1 is associated with kinases, L1-L1 binding regulates second messenger systems, and mutations in the L1 gene in humans result in abnormalities in the development of the corticospinal tract and corpus callosum. In this short review, recent advances in understanding the way in which L1 regulates growth cone behavior will be discussed.

Animals↗
PubMed1991

Purification, characterization and mechanism of action of scatter factor from human placenta.

Scatter factor (SF) causes contiguous sheets of epithelium to spread and cells to separate from each other. SF also increases the velocity, area, and reduces the circularity of individual cells. These changes are mediated in part by alterations in protein synthesis, protein phosphorylation, cytoskeletal reorganization, and cell surface components. SF has been purified from the conditioned medium of ras transformed 3T3 cells and human placenta. Sequence information suggests that SF from 3T3 cells is closely related to hepatocyte growth factor. SF is a glycoprotein, but glycosylation is not necessary for its activity. Glycosylation of target cell proteins, however, is required for SF action.

Animals↗
PubMed1987

Cellular signal transduction and the reversal of malignancy.

Animal cells contain only a few defined molecular systems that transduce hormonal and growth signals from the external environment to the intracellular milieu to regulate cellular growth and differentiation. Among the most ubiquitous of these "second messenger" pathways are those utilizing cyclic AMP and phosphatidylinositide turnover. The former activates protein kinase A, while the latter leads to the activation of protein kinase C and mobilization of intracellular calcium. Lesions induced by oncogenes in signal transduction systems may be responsible for the cancerous transformation of cells. In many tumor cell lines, including some transformed by the ras and sis oncogenes, activation of protein kinase A by elevation of cyclic AMP or activation of protein kinase C by addition of phorbol esters can restore many normal aspects of growth and morphology. Such "reverse transformation" is accompanied by the phosphorylation of unique cellular proteins and alterations in the phosphoinositide cycle. Molecular mechanisms by which activation of signal transduction systems can attenuate the malignant phenotype are considered in the context of cellular growth and differentiation.

Animals↗
PubMed1980

Polarized distribution of viral envelope proteins in the plasma membrane of infected epithelial cells.

The surface distribution of the envelope glycoproteins of influenza, Sendai and Vesicular Stomatitis viruses was studied by immunofluorescence and immunoelectromicroscopy in infected epithelial cell monolayers, from which these viruses bud in a polarized fashion. It was found that before the onset of viral budding, the envelope proteins are exclusively localized into the same plasma membrane domains of the epithelial cells from which the virions ultimately bud: the glycoproteins of influenza and Sendai were detected at the apical surface, while the G protein of Vesicular Stomatitis virus was concentrated at the basolateral region. On the other hand, Sendai virus nucleocapsids, which can be easily identified in the cytoplasm before viral assembly, could be observed throughout the cell, not showing any preferential localization near the surface that the virions utilize for budding. These results are consistent with a model in which the asymmetric distribution of viral envelope proteins, rather than a polarized delivery of nucleocapsids, directs the polarity of viral budding. Furthermore, the asymmetric surface localization of viral glycoproteins suggests that these proteins share with intrinsic surface proteins of epithelial cells common biogenetic mechanisms and informational features or "sorting out" signals that determine their compartmentalization in the plasma membrane.

Animals↗
PubMed1974

Localization of Escherichia coli ribosomal proteins S4 and S14 by electron microscopy of antibody-labeled subunits.

Binding sites for antibodies specific for proteins S4 and S14 of the small subunit of E. coli ribosomes have been mapped on the surface of the subunit by electron microscopy. Antibody binding to reconstituted subunits was shown to depend specifically on the presence of E. coli S4 and S14. Anti-S14 IgG was found to bind to a limited region of the ribosome surface. In contrast anti-S4 IgG was found to bind to three separated regions of the ribosome surface, suggesting S4 has an elongated conformation in situ.

Bacterial Proteins↗