Coupling geometric PDEs with physics, cell morphology, motility and pattern formation

Annual report on the 6-months research programme held at the Isaac Newton Institute for Mathematical Sciences on Coupling geometric PDEs with physics for cell morphology, motility and pattern formation from July 13th - December 18th 201

Keratin Dynamics: Modeling the Interplay between Turnover and Transport

Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data. Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the assembled keratin is required to explain the experimentally observed keratin organization.Comment: 27 pages, 11 Figure

Synaptophysin Is Required for Synaptobrevin Retrieval during Synaptic Vesicle Endocytosis

The integral synaptic vesicle (SV) protein synaptophysin forms approximately 10% of total SV protein content, but has no known function in SV physiology. Synaptobrevin (sybII) is another abundant integral SV protein with an essential role in SV exocytosis. Synaptophysin and sybII form a complex in nerve terminals, suggesting this interaction may have a key role in presynaptic function. To determine how synaptophysin controls sybII traffic in nerve terminals, we used a combination of optical imaging techniques in cultures derived from synaptophysin knockout mice. We show that synaptophysin is specifically required for the retrieval of the pH-sensitive fluorescent reporter sybII-pHluorin from the plasma membrane during endocytosis. The retrieval of other SV protein cargo reporters still occurred, however their recapture proceeded with slower kinetics. This slowing of SV retrieval kinetics in the absence of synaptophysin did not impact on global SV turnover. These results identify a specific and selective requirement for synaptophysin in the retrieval of sybII during SV endocytosis and suggest that their interaction may act as an adjustable regulator of SV retrieval efficiency

Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia

Epithelia are exposed to multiple forms of stress. Keratin intermediate filaments are abundant in epithelia and form cytoskeletal networks that contribute to cell type–specific functions, such as adhesion, migration, and metabolism. A perpetual keratin filament turnover cycle supports these functions. This multistep process keeps the cytoskeleton in motion, facilitating rapid and protein biosynthesis–independent network remodeling while maintaining an intact network. The current challenge is to unravel the molecular mechanisms underlying the regulation of the keratin cycle in relation to actin and microtubule networks and in the context of epithelial tissue function

Social and individual features affecting natal dispersal in the colonial Lesser Kestrel

Causes of natal dispersal were studied in an isolated population of the migratory, facultatively colonial Lesser Kestrel (Falco naumanni) in northeastern Spain. During a seven-year study, we gathered information on natal dispersal of 751 individuals and on 24 explanatory variables that evaluated individual traits, conspecific cues in terms of colony size, and different ecological and populational features. We examined separately whether or not individuals changed colonies and how far they moved. Dispersal from the natal colony was high (83%), and dispersers covered a median distance of 7225 m (range 112-136 500 m). The probability of natal dispersal decreased with the size of the natal colony and with the distance to the nearest colony, but not with the distance to unoccupied buildings, in the year of recruitment. Moreover, the shorter the distance to the nearest colony, the shorter the distances that individuals dispersed, particularly to large colonies (>10 pairs). These results support the conspecific attraction hypothesis. Accordingly, the probability of recruiting in the natal colony increased with the proportion of philopatric adults, although beyond a threshold individuals were prevented from recruiting by the more dominant adults in a despotic way. The timing of arrival from the wintering grounds was positively related to the probability of colony change, especially in males. To the extent that this variable is related to the phenotypic quality of individuals, it reinforces the idea that natal dispersal is shaped by intraspecific competition in crowded colonies. Males showed lower frequencies of colony change and dispersed shorter distances than did females, as explained by the different role of the sexes in nest acquisition and defense. Our results indicate that natal dispersal is an evolutionarily labile trait simultaneously influenced by ecological, social, and individual features both within and between populations.Peer Reviewe

Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions

Intermediate filaments (IFs) are major components of the metazoan cytoskeleton. A long-standing debate concerns the question whether IF network organization only reflects or also determines cell and tissue function. Using Caenorhabditis elegans, we have recently described mutants of the mitogen-activated protein kinase (MAPK) SMA-5 which perturb the organization of the intestinal IF cytoskeleton resulting in luminal widening and cytoplasmic invaginations. Besides these structural phenotypes, systemic dysfunctions were also observed. We now identify the IF polypeptide IFB-2 as a highly efficient suppressor of both the structural and functional deficiencies of mutant sma-5 animals by removing the aberrant IF network. Mechanistically, perturbed IF network morphogenesis is linked to hyperphosphorylation of multiple sites throughout the entire IFB-2 molecule. The rescuing capability is IF isotype-specific and not restricted to sma-5 mutants but extends to mutants that disrupt the function of the cytoskeletal linker IFO-1 and the IF-associated protein BBLN-1. The findings provide strong evidence for adverse consequences of the deranged IF networks with implications for diseases that are characterized by altered IF network organization