Fundación Instituto Leloir

About: Fundación Instituto Leloir is a facility organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Dentate gyrus & Neurogenesis. The organization has 702 authors who have published 1052 publications receiving 39299 citations.

Time-Resolved Energetics of Photoprocesses in Prokaryotic Phytochrome-Related Photoreceptors

Abstract: Time-resolved photoacoustics (PA) is uniquely able to explore the energy landscape of photoactive proteins and concomitantly detects light-induced volumetric changes (ΔV) accompanying the formation and decay of transient species in a time window between ca. 20 ns and 5 μs. Here, we report PA measurements on diverse photochromic bilin-binding photoreceptors of prokaryotic origin: (1) the chromophore-binding GAF3 domain of the red (R)/green (G) switching cyanobacteriochrome 1393 (Slr1393g3) from Synechocystis; (2) the red/far red (R/FR) Synechocystis Cph1 phytochrome; (3) full-length and truncated constructs of Xanthomonas campestris bacteriophytochrome (XccBphP), absorbing up to the NIR spectral region. In almost all cases, photoisomerization results in a large fraction of energy dissipated as heat (up to 90%) on the sub-ns scale, reflecting the low photoisomerization quantum yield (<0.2). This "prompt" step is accompanied by a positive ΔV1 = 5-12.5 mL mol-1 . Formation of the first intermediate is the sole process accessible to PA, with the notable exception of Slr1393g3-G for which ΔV1 = +4.5 mL mol-1 is followed by a time-resolved, energy-conserving contraction ΔV2 = -11.4 mL mol-1 , τ2 = 180 ns at 2.4°C. This peculiarity is possibly due to a larger solvent occupancy of the chromophore cavity for Slr1393g3-G.

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons

Abstract: The dentate gyrus of the hippocampus is dominated by a strong GABAergic tone that maintains sparse levels of activity. Adult neurogenesis disrupts this balance through the continuous addition of new granule cells (GCs) that display high excitability while develop and connect within the preexisting host circuit. The dynamics of the connectivity map for developing GCs in the local inhibitory networks remains unknown. We used optogenetics to study afferent and efferent synaptogenesis between new GCs and GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs). Inputs from PV-INs targeted the soma and remained immature until they grew abruptly in >4-week-old GCs. This transition was accelerated by exposure to enriched environment. Inputs from SST-INs were dendritic and developed slowly until reaching maturity by 8 weeks. Synaptic outputs from GCs onto PV-INs matured faster than those onto SST-INs, but also required several weeks. In the mature dentate network, PV-INs exerted an efficient control of GC spiking and were involved in both feedforward and feedback loops, a mechanism that would favor lateral inhibition and sparse coding. Our results reveal a long-lasting transition where adult-born neurons remain poorly coupled to inhibition, which might enable a parallel streaming channel from the entorhinal cortex to CA3 pyramidal cells.

Novel mRNA-silencing bodies at the synapse: A never-ending story.

Abstract: Several cellular responses depend on translational regulation and in most cases, this involves the formation of cytoplasmic granules that contain repressed mRNAs. In neurons, numerous mRNAs travel along dendrites to be locally regulated upon synapse activity and we have recently shown that the exoribonuclease XRN1 forms dynamic aggregates at the post synapse that respond to specific stimuli.1 These foci were termed SX-bodies and are distinct from stress granules (SGs), processing bodies (PBs) and other RNA granules previously described. Together with Smaug1-foci and FMRP-granules, the SX-bodies contribute to dynamically shape the transcriptome available for translation at the post-synapse.

Chasing coevolutionary signals in intrinsically disordered proteins complexes

Abstract: Intrinsically disordered proteins/regions (IDPs/IDRs) are crucial components of the cell, they are highly abundant and participate ubiquitously in a wide range of biological functions, such as regulatory processes and cell signaling. Many of their important functions rely on protein interactions, by which they trigger or modulate different pathways. Sequence covariation, a powerful tool for protein contact prediction, has been applied successfully to predict protein structure and to identify protein-protein interactions mostly of globular proteins. IDPs/IDRs also mediate a plethora of protein-protein interactions, highlighting the importance of addressing sequence covariation-based inter-protein contact prediction of this class of proteins. Despite their importance, a systematic approach to analyze the covariation phenomena of intrinsically disordered proteins and their complexes is still missing. Here we carry out a comprehensive critical assessment of coevolution-based contact prediction in IDP/IDR complexes and detail the challenges and possible limitations that emerge from their analysis. We found that the coevolutionary signal is faint in most of the complexes of disordered proteins but positively correlates with the interface size and binding affinity between partners. In addition, we discuss the state-of-art methodology by biological interpretation of the results, formulate evaluation guidelines and suggest future directions of development to the field.