RESUMEN
É£-aminobutyric acid (GABA) is a fourcarbon amino acid acting as the main inhibitory transmitter in the invertebrate and vertebrate nervous systems. The metabolism of GABA is well compartmentalized in the cell and the uptake of cytosolic GABA into the mitochondrial matrix is required for its degradation. A previous study carried out in the fruit fly Drosophila melanogaster indicated that the mitochondrial aspartate/glutamate carrier (AGC) is responsible for mitochondrial GABA accumulation. Here, we investigated the transport of GABA catalysed by the human and D. melanogaster AGC proteins through a well-established method for the study of the substrate specificity and the kinetic parameters of the mitochondrial carriers. In this experimental system, the D. melanogaster spliced AGC isoforms (Aralar1-PA and Aralar1-PE) and the human AGC isoforms (AGC1/aralar1 and AGC2/citrin) are unable to transport GABA both in homo- and in hetero-exchange with either glutamate or aspartate, i.e. the canonical substrates of AGC. Moreover, GABA has no inhibitory effect on the exchange activities catalysed by the investigated AGCs. Our data demonstrate that AGC does not transport GABA and the molecular identity of the GABA transporter in human and D. melanogaster mitochondria remains unknown.
RESUMEN
The biological functions of the scaffold protein Ran Binding Protein 9 (RanBP9) remain elusive in macrophages or any other cell type where this protein is expressed together with its CTLH (C-terminal to LisH) complex partners. We have engineered a new mouse model, named RanBP9-TurnX, where RanBP9 fused to three copies of the HA tag (RanBP9-3xHA) can be turned into RanBP9-V5 tagged upon Cre-mediated recombination. We created this model to enable stringent biochemical studies at cell type specific level throughout the entire organism. Here, we have used this tool crossed with LysM-Cre transgenic mice to identify RanBP9 interactions in lung macrophages. We show that RanBP9-V5 and RanBP9-3xHA can be both co-immunoprecipitated with the known members of the CTLH complex from the same whole lung lysates. However, more than ninety percent of the proteins pulled down by RanBP9-V5 differ from those pulled-down by RanBP9-HA. The lung RanBP9-V5 associated proteome includes previously unknown interactions with macrophage-specific proteins as well as with players of the innate immune response, DNA damage response, metabolism, and mitochondrial function. This work provides the first lung specific RanBP9-associated interactome in physiological conditions and reveals that RanBP9 and the CTLH complex could be key regulators of macrophage bioenergetics and immune functions.
RESUMEN
Hyaluronic acid (HA) naturally occurs as a biopolymer in the human body, primarily in connective tissues like joints and skin. Functioning as a vital element of synovial fluid, it lubricates joints, facilitating fluid movement and diminishing bone friction to protect articular well-being. Its distinctive attributes encompass notable viscosity and water retention capacities, ensuring flexibility and absorbing shock during motion. Furthermore, HA has gained significant attention for its potential benefits in various medical applications, including rehabilitation. Ongoing research explores its properties and functions, especially its biomedical applications in several clinical trials, with a focus on its role in improving rehabilitation outcomes. But the clinical and biochemical implications of HA in musculoskeletal rehabilitation have yet to be fully explored. This review thoroughly investigates the properties and functions of HA while highlighting its biomedical applications in different clinical trials, with a special emphasis on its role in rehabilitation. The presented findings provide evidence that HA, as a natural substance, enhances the outcomes of musculoskeletal rehabilitation through its exceptional mechanical and biochemical effects.