Biology of the Cell

The Golgi apparatus in the endomembrane-rich gastric parietal cells exist as functional stable mini-stacks dispersed throughout the cytoplasm

2011-12-01

Background information. Acid-secreting gastric parietal cells are polarized epithelial cells that harbour highly abundant and specialized, H⁺,K⁺ ATPase-containing, tubulovesicular membranes in the apical cytoplasm. The Golgi apparatus has been implicated in the biogenesis of the tubulovesicular membranes; however, an unanswered question is how a typical Golgi organization could regulate normal membrane transport within the membrane-dense cytoplasm of parietal cells.

Results. Here, we demonstrate that the Golgi apparatus of parietal cells is not the typical juxta-nuclear ribbon of stacks, but rather individual Golgi units are scattered throughout the cytoplasm. The Golgi membrane structures labelled with markers of both cis- and trans-Golgi membrane, indicating the presence of intact Golgi stacks. The parietal cell Golgi stacks were closely aligned with the microtubule network and were shown to participate in both anterograde and retrograde transport pathways. Dispersed Golgi stacks were also observed in parietal cells from H⁺,K⁺ ATPase-deficient mice that lack tubulovesicular membranes.

Conclusions. These results indicate that the unusual organization of individual Golgi stacks dispersed throughout the cytoplasm of these terminally differentiated cells is likely to be a developmentally regulated event.

Defining the role of TRIP6 in cell physiology and cancer

2011-12-01

Integrating signals from the ECM (extracellular matrix) via the cell surface into the nucleus is an essential feature of multicellular life and often malfunctions in cancer. To date many signal transducers known as shuttle proteins have been identified that act as both: a cytoskeletal and a signalling protein. Here, we highlight the interesting member of the Zyxin family TRIP6 [thyroid receptor interactor protein 6; also designated ZRP-1 (zyxin-related protein 1)] and review current literature to define its role in cell physiology and cancer. TRIP6 is a versatile scaffolding protein at FAs (focal adhesions) involved in cytoskeletal organization, coordinated cell migration and tissue invasion. Via its LIM and TDC domains TRIP6 interacts with different components of the LPA (lysophosphatidic acid), NF-κB (nuclear factor κB), glucocorticoid and AMPK (AMP-activated protein kinase) signalling pathway and thereby modulates their activity. Within the nucleus TRIP6 acts as a transcriptional cofactor regulating the transcriptional responses of these pathways. Moreover, intranuclear TRIP6 associates with proteins ensuring telomere protection and hence may contribute to genome stability. Accordingly, TRIP6 is engaged in key cellular processes such as cell proliferation, differentiation and survival. These diverse functions of TRIP6 are found to be dysregulated in various cancers and may have pleiotropic roles in tumour initiation, tumour growth and metastasis, which turn TRIP6 into an attractive candidate for cancer diagnosis and targeted therapy.

Jumping the barrier: VE-cadherin, VEGF and other angiogenic modifiers in cancer

Armelle Le Guelte, Julie Dwyer and Julie Gavard — 2011-12-01

The endothelial barrier controls the passage of fluids, nutrients and cells through the vascular wall. This physiological function is closely related to developmental and adult angiogenesis, blood pressure control, as well as immune responses. Moreover, cancer progression is frequently characterized by disorganized and leaky blood vessels. In this context, vascular permeability drives tumour-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration and tumour cell extravasation. Although various molecules have been implicated, the vascular endothelial adhesion molecule, VE-cadherin (vascular endothelial cadherin), has emerged as a critical player involved in maintaining endothelial barrier integrity and homoeostasis. Indeed, VE-cadherin coordinates the endothelial cell-cell junctions through its adhesive and signalling properties. Of note, many angiogenic and inflammatory mediators released into the tumour microenvironment influence VE-cadherin behaviour. Therefore restoring VE-cadherin function could be one very promising target for vascular normalization in cancer therapies. In this review, we will mainly focus on recent discoveries concerning the molecular mechanisms involved in modulating VE-cadherin plasticity in cancer.

Characterization of a novel angiogenic model based on stable, fluorescently labelled endothelial cell lines amenable to scale-up for high content screening

2011-12-01