Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

The UMAG_00031 gene from Ustilago maydis encodes a putative membrane protein involved in pH control and morphogenesis.

We report the characterization of the gene UMAG_00031 from Ustilago maydis, previously identified as upregulated at alkaline pH. This gene is located on chromosome 1 and contains an ORF of 1539 bp that encodes a putative protein of 512 amino acids with an MW of 54.8 kDa. The protein is predicted to contain seven transmembrane domains (TMDs) and a signal peptide suggesting that is located in the cell membrane. Null ΔUMAG_00031 mutants were constructed, and their phenotype was analyzed. The mutant displayed a pleiotropic phenotype suggesting its participation in processes of alkaline pH adaptation independent of the Pal/Rim pathway. Also, it was involved in the dimorphic process induced by fatty acids. These results indicate that the protein encoded by the UMAG_00031 gene possibly functions as a receptor of different signals in the cell membrane of the fungus.

Adaptation of Ustilago maydis to extreme pH values: A transcriptomic analysis.

Fungi are capable to adapt to environments with different pH values. Here we used microarrays to analyze the transcriptomic response of the Basidiomycota Ustilago maydis when transferred from a neutral pH medium to acidic, or alkaline media. Yeast and hyphal monomorphic mutants were used as controls, permitting the identification of 301 genes differentially regulated during the transfer from neutral to an acidic medium, of which 162 were up-regulated and 139 down-regulated. When cells were transferred to an alkaline medium, we identified 797 differentially regulated genes, 335 up-regulated, and 462 down-regulated. The category showing the highest number of regulated genes during the change to either pH, besides "unclassified," was "metabolism," indicating that a very important factor for adaptation is a change in the metabolic machinery. These data reveal that adaptation of U. maydis to environments with different pH involves a severe modification of the transcription machinery to cope with the new conditions, and that the stress by an alkaline environment is more drastic than a change to an acidic medium. The data also revealed that only a minor proportion of the identified genes are under the apparent control of the Pal/Rim pathway, indicating that pH adaptation of this fungus involves other than this cannonical pathway.