A new look at transudation: the apocrine connection.

Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this term has been used synonymously with transudation. In both cases transcellular trafficking starts with the internalization of proteins or other compounds on the basal or basolateral side of a cell and continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. This allows a cell to release products which are synthesized elsewhere. Here, we discuss the common features of both transcytosis and transudation, and that which differentiates them. It appears that transcytosis and transudation are identical in terms of vesicular import and endosomal sorting of cargo, but completely differ in the re-secretion process. Specialized epithelial cells re-release substantial quantities of the endocytosed material, and often also a great variety. Some recent studies indicate that this is achieved by non-canonical apocrine secretion rather than by the regular vesicular mechanism of exocytosis, and takes place only on the apical pole. This massive re-release of endocytosed proteins, and potentially other compounds via the apocrine mechanism should be considered as transudation, distinct from transcytosis.

A fraction of MCM 2 proteins remain associated with replication foci during a major part of S phase.

The essential role of MCM 2-7 proteins in the initiation of DNA replication in all eukaryotes is well known. Their role in replication elongation is supported by numerous studies, but there is still a knowledge gap in this respect. Even though biochemical studies have established an association of MCM proteins with replication forks, previous immunofluorescence studies in mammalian cells have suggested that MCM 2-7 proteins are displaced after replication initiation from sites of DNA replication. Therefore, we used a robust statistical method to more precisely analyse immunofluorescence localization of MCM 2 proteins with respect to the DNA replication foci. We show that despite the predominantly different localization of MCM 2 and replication signals, there is still a small but significant fraction of MCM 2 proteins that co-localize with DNA replication foci during most of S phase. The fluorescence localization of the MCM 2 proteins and DNA replication may thus reflect an active function of MCM 2 proteins associated with the replication foci and partially explain one facet of the "MCM paradox".

SMED-TLX-1 (NR2E1) is critical for tissue and body plan maintenance in Schmidtea mediterranea in fasting/feeding cycles.

Nuclear receptors (NRs), or nuclear hormone receptors (NHRs), are transcription factors that regulate development and metabolism of most if not all animal species. Their regulatory networks include conserved mechanisms that are shared in-between species as well as mechanisms that are restricted to certain phyla or even species. In search for conserved members of the NHR family in Schmidtea mediterranea, we identified a molecular signature of a class of NRs, NR2E1, in the S. mediterranea genome and cloned its complete cDNA coding sequence. The derived amino acid sequence shows a high degree of conservation of both DNA-binding domain and ligand- binding domain and a remarkably high homology to vertebrate NR2E1 and C. elegans NHR-67. Quantitative PCR detected approximately ten-fold higher expression of Smed-tlx-1 in the proximal part of the head compared to the tail region. The expression of Smed-tlx-1 is higher during fed state than during fasting. Smed-tlx-1 down-regulation by RNA interference affects the ability of the animals to maintain body plan and induces defects of brain, eyes and body shape during fasting and re-growing cycles. These results suggest that SMED-TLX-1 is critical for tissue and body plan maintenance in planaria.

Bone metabolism: a note on the significance of mouse models.

This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possible limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing unforeseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other.