Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/R.B.M. was a recipient of a UK Medical Research Council (MRC) studentship, MRC Centenary Award, Barts and The London Charity (472/1711) and Rosetrees Trust (M314), N.K. was a recipient of an MRC studentship (MR/J500409/1), C.J. was a recipient of the Barts and The London Charitable Foundation Scholarship (RAB 05/PJ/07), L.M. was supported by CR-UK, Breast Cancer Now (2008NovPR10) and Rosetrees Trust (M346), A.H. was a recipient of a CR-UK studentship (C236/A11795). P.J.P. was supported by CR-UK. J.I. was supported by grants from the Academy of Finland, ERC Starting grant, Finnish Cancer Organisations and Sigrid Juselius Foundation. S.K. was supported by the MRC (G0501003) and The British Lung Foundation (CAN09-4)

Computational Methods for Protein Identification from Mass Spectrometry Data

Protein identification using mass spectrometry is an indispensable computational tool in the life sciences. A dramatic increase in the use of proteomic strategies to understand the biology of living systems generates an ongoing need for more effective, efficient, and accurate computational methods for protein identification. A wide range of computational methods, each with various implementations, are available to complement different proteomic approaches. A solid knowledge of the range of algorithms available and, more critically, the accuracy and effectiveness of these techniques is essential to ensure as many of the proteins as possible, within any particular experiment, are correctly identified. Here, we undertake a systematic review of the currently available methods and algorithms for interpreting, managing, and analyzing biological data associated with protein identification. We summarize the advances in computational solutions as they have responded to corresponding advances in mass spectrometry hardware. The evolution of scoring algorithms and metrics for automated protein identification are also discussed with a focus on the relative performance of different techniques. We also consider the relative advantages and limitations of different techniques in particular biological contexts. Finally, we present our perspective on future developments in the area of computational protein identification by considering the most recent literature on new and promising approaches to the problem as well as identifying areas yet to be explored and the potential application of methods from other areas of computational biology

Rotranslational dynamics of confined water. II. Spectroscopic evidence of confinement effects on the far-infrared spectra of water isotopologues in argon and krypton matrices

International audienceWater molecules trapped in rare gas matrices exhibit conspicuous shifts in their far-infrared (FIR), rotranslational spectral features compared with the corresponding transitions observed in the gas phase. These confinement-induced perturbations have been related not only to the quantization of translational motion but also to the coupling between the orientational and positional degrees of freedom: the rotation-translation coupling (RTC). As the propensity displayed by the nuclear spin isomers (NSI) of water to undergo interconversion in confinement is intimately related to how its nuclear spin degrees of freedom are coupled with those for intra- and intermolecular motions, confinement-induced RTC should also strongly impact the NSI interconversion mechanisms and rates. Insight into the rotranslational dynamics for H216O, H217O, and H218O, confined in argon and krypton matrices, is provided here based on the evolution of rotranslational spectra induced by NSI interconversion while a definitive assignment is provided from the transition energies and intensities calculated using the confined rotor model [Paper I, Wespiser et al., J. Chem. Phys. 156, 074304 (2021)]. In order to build a complete rotranslational energy diagram of confined water, which is fundamental to understand the NSI interconversion rates, the energy difference between the ground ortho and para rotranslational states is derived from the temperature dependence of the intensity ratio of mid-infrared lines emerging from these states. These investigations should provide deeper insight of the factors that control NSI interconversion of water isotopologues under extreme confinement

NBR 1 enables autophagy-dependent focal adhesion turnover

Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRC A1 (NBR 1) as a key mediator of autophagy-dependent FA remodeling. NBR 1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR 1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR 1-mediated selective autophagy in enabling FA disassembly in motile cells