Neuroblastoma Tyrosine Kinase Signaling Networks Involve FYN and LYN in Endosomes and Lipid Rafts

Protein phosphorylation plays a central role in creating a highly dynamic network of interacting proteins that reads and responds to signals from growth factors in the cellular microenvironment. Cells of the neural crest employ multiple signaling mechanisms to control migration and differentiation during development. It is known that defects in these mechanisms cause neuroblastoma, but how multiple signaling pathways interact to govern cell behavior is unknown. In a phosphoproteomic study of neuroblastoma cell lines and cell fractions, including endosomes and detergent-resistant membranes, 1622 phosphorylated proteins were detected, including more than half of the receptor tyrosine kinases in the human genome. Data were analyzed using a combination of graph theory and pattern recognition techniques that resolve data structure into networks that incorporate statistical relationships and protein-protein interaction data. Clusters of proteins in these networks are indicative of functional signaling pathways. The analysis indicates that receptor tyrosine kinases are functionally compartmentalized into distinct collaborative groups distinguished by activation and intracellular localization of SRC-family kinases, especially FYN and LYN. Changes in intracellular localization of activated FYN and LYN were observed in response to stimulation of the receptor tyrosine kinases, ALK and KIT. The results suggest a mechanism to distinguish signaling responses to activation of different receptors, or combinations of receptors, that govern the behavior of the neural crest, which gives rise to neuroblastoma.     

Toward a phylogeny and biogeography of Diaphanosoma (Crustacea: Cladocera)

Aquatic Ecology - Diaphanosoma s.l., with 40+? described species, is the largest genus of the Sididae and the Ctenopoda, similar in many ways to the anomopod genus Daphnia. Here, we offer a c...     

Microbulbifer hainanensis sp. nov., a moderately halopilic bacterium isolated from mangrove sediment

Antonie van Leeuwenhoek - A new bacterium was successfully isolated from a mangrove sediment sample in Haikou City, Hainan Province, China. The organism is a Gram-negative, rod-shaped, non-motile...     

Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway

The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Lats1/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase CRL4^DCAF1. Numerous mutations of Merlin have been identified in Neurofibromatosis type 2 and other cancer patients. Despite more than two decades of research, the upstream regulator of Merlin in the Hippo pathway remains unknown. Here we show by high-resolution crystal structures that the Lats1/2-binding site on the Merlin FERM domain is physically blocked by Merlin''s auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and promotes Merlin''s binding to Lats1/2. Phosphorylation of Ser518 outside the Merlin''s auto-inhibitory tail does not obviously alter Merlin''s conformation, but instead prevents angiomotin from binding and thus inhibits Hippo pathway kinase activation. Cancer-causing mutations clustered in the angiomotin-binding domain impair angiomotin-mediated Merlin activation. Our findings reveal that angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling, and allow construction of a complete Hippo signaling pathway.     

A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles,geography and ethnicities

Structural profiling of healthy human gut microbiota across heterogeneous populations is necessary for benchmarking and characterizing the potential ecosystem services provided by particular gut symbionts for maintaining the health of their hosts. Here we performed a large structural survey of fecal microbiota in 314 healthy young adults, covering 20 rural and urban cohorts from 7 ethnic groups living in 9 provinces throughout China. Canonical analysis of unweighted UniFrac principal coordinates clustered the subjects mainly by their ethnicities/geography and less so by lifestyles. Nine predominant genera, all of which are known to contain short-chain fatty acid producers, co-occurred in all individuals and collectively represented nearly half of the total sequences. Interestingly, species-level compositional profiles within these nine genera still discriminated the subjects according to their ethnicities/geography and lifestyles. Therefore, a phylogenetically diverse core of gut microbiota at the genus level may be commonly shared by distinctive healthy populations as functionally indispensable ecosystem service providers for the hosts.