Organization of Physical Interactomes as Uncovered by Network Schemas

Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks

Causes and consequences of mass loss upon predator encounter: feeding interruption, stress or fit-for-flight?

1. Birds have been shown to lose mass upon predator encounters. This mass loss has generally been assumed to be caused by the feeding interruption the birds experience upon encountering the predator. However, birds may lose this mass because of predator stress and because they prepare themselves for flight (fit-for-flight). In this experiment the aim was to distinguish between effects of feeding interruptions and stress or fit-for-flight on the mass loss of Yellowhammers (Emberiza citrinella L.) upon predator exposure. 2. When exposed to a 45-min feeding interruption, the birds lost only a quarter of the mass they lost when they were moved to another room and exposed to a stuffed Sparrowhawk (Accipiter nisus) for 1 min at that beginning of the feeding interruption. This indicates that mass loss upon predator exposure is not just due to the feeding interruption birds experience upon encountering a predator, but is probably, to a large extent, due to both predator stress and fit-for-flight. 3. When the stuffed Sparrowhawk was replaced with a dummy (an opaque plastic bottle), mass loss upon exposure was similar to the loss in the Sparrowhawk treatment. This indicates that moving the birds to another room, which occurred in both these treatments, may to a large extent be the cause of the mass loss. 4. During the same day, the birds regained 92% of their losses. However, regaining those losses was partly postponed to the end of the day, which indicates that the birds faced a trade-off between starvation and predation risk, and were able to respond to that trade-off by altering their diurnal trajectory of mass increase. By postponing foraging to the end of the day, the birds decreased the mass-dependent costs of predation risk

Alpha-synuclein: from secretion to dysfunction and death

The aggregation, deposition, and dysfunction of alpha-synuclein (aSyn) are common events in neurodegenerative disorders known as synucleinopathies. These include Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. A growing body of knowledge on the biology of aSyn is emerging and enabling novel hypotheses to be tested. In particular, the hypothesis that aSyn is secreted from neurons, thus contributing to the spreading of pathology not only in the brain but also in other organs, is gaining momentum. Nevertheless, the precise mechanism(s) of secretion, as well as the consequences of extracellular aSyn species for neighboring cells are still unclear. Here, we review the current literature and integrate existing data in order to propose possible mechanisms of secretion, cell dysfunction, and death. Ultimately, the complete understanding of these processes might open novel avenues for the development of new therapeutic strategies

Inheritance and biogenesis of organelles in the secretory pathway.

In eukaryotic cells, cellular functions are compartmentalized into membrane-bound organelles. This has many advantages, as shown by the success of the eukaryotic lineage, but creates many problems for cells, such as the need to build and partition these organelles during cell growth and division. Diverse mechanisms for biogenesis of the endoplasmic reticulum and Golgi apparatus have evolved, ranging from de novo synthesis to the copying of a template organelle. The different mechanisms by which organelles are inherited in yeasts, protozoa and metazoans probably reflect the differences in the structure and copy number of these organelles