Loss of growth homeostasis by genetic decoupling of cell division from biomass growth: implication for size control mechanisms.

Growing cells adjust their division time with biomass accumulation to maintain growth homeostasis. Size control mechanisms, such as the size checkpoint, provide an inherent coupling of growth and division by gating certain cell cycle transitions based on cell size. We describe genetic manipulations that decouple cell division from cell size, leading to the loss of growth homeostasis, with cells becoming progressively smaller or progressively larger until arresting.

Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity.

Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance. A distinct feature of promiscuous gene expression is its mosaic pattern (i.e.

Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists.

Bone morphogenetic proteins (BMPs) are members of the TGFβ family of signaling proteins and play an important role during development and in tissue formation. BMP signaling is a well-studied process, which is initiated through binding of cognate receptors and processed through activation of Smad downstream mediators. A hallmark of BMP signaling is its modulation at the extracellular level through specific antagonists.

Multiparametric image analysis reveals role of Caveolin1 in endosomal progression rather than internalization of EGFR.

Endosomes constitute a central layer in the regulation of growth factor signaling. We applied flow cytometry, confocal microscopy and automated image quantification to define the role of Caveolin1 (Cav1) in epidermal growth factor (EGF) receptor (i) internalization and (ii) endosomal trafficking. Antisense-downregulation of Cav1 did not affect internalization of EGF:EGFR-complexes from the plasma membrane.

Reorganization of gap junctions after focused ultrasound blood-brain barrier opening in the rat brain.

Ultrasound-induced opening of the blood-brain barrier (BBB) is an emerging technique for targeted drug delivery to the central nervous system. Gap junctions allow transfer of information between adjacent cells and are responsible for tissue homeostasis. We examined the effect of ultrasound-induced BBB opening on the structure of gap junctions in cortical neurons, expressing Connexin 36, and astrocytes, expressing Connexin 43, after focused 1-MHz ultrasound exposure at 1.

Systems biological analysis of epidermal growth factor receptor internalization dynamics for altered receptor levels.

Epidermal growth factor (EGF) receptor (EGFR) overexpression is a hallmark of many cancers. EGFR endocytosis is a critical step in signal attenuation, raising the question of how receptor expression levels affect the internalization process. Here we combined quantitative experimental and mathematical modeling approaches to investigate the role of the EGFR expression level on the rate of receptor internalization.

An ultrasensitive sorting mechanism for EGF receptor endocytosis.

Background: The Epidermal Growth Factor (EGF) receptor has been shown to internalize via clathrin-independent endocytosis (CIE) in a ligand concentration dependent manner. From a modeling point of view, this resembles an ultrasensitive response, which is the ability of signaling networks to suppress a response for low input values and to increase to a pre-defined level for inputs exceeding a certain threshold. Several mechanisms to generate this behaviour have been described theoretically, the underlying assumptions of which, however, have not been experimentally demonstrated for the EGF receptor internalization network.