Publications by authors named "Laura Perez-Guardia"

Store-operated Ca entry (SOCE) controls Ca homeostasis and mediates multiple Ca-dependent signaling pathways and cellular processes. It relies on the concerted activity of the reticular Ca sensor STIM1 and the plasma membrane Ca channel ORAI1. STIM1 and ORAI1 gain-of-function (GoF) mutations induce SOCE overactivity and excessive Ca influx, leading to tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK), two overlapping disorders characterized by muscle weakness and a variable occurrence of multi-systemic anomalies affecting spleen, skin, and platelets.

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Article Synopsis
  • * Experimental mouse models showed that pairing a TAM mutation (Stim1R304W) with a partial ORAI1 mutation (Orai1R93W) led to positive health outcomes, including improved bone structure, spleen health, muscle function, and increased platelet counts.
  • * The study suggests that targeting ORAI1 could offer a potential treatment strategy for TAM/STRMK, and identified myostatin as a potential biom
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Aims: Limb-girdle congenital myasthenic syndrome (LG-CMS) is a genetically heterogeneous disorder characterized by muscle weakness and fatigability. The LG-CMS gene DPAGT1 codes for an essential enzyme of the glycosylation pathway, a posttranslational modification mechanism shaping the structure and function of proteins. In DPAGT1-related LG-CMS, reduced glycosylation of the acetylcholine receptor (AChR) reduces its localization at the neuromuscular junction (NMJ), and results in diminished neuromuscular transmission.

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Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) form a clinical continuum associating progressive muscle weakness with additional multi-systemic anomalies of the bones, skin, spleen, and platelets. TAM/STRMK arises from excessive extracellular Ca entry due to gain-of-function mutations in the Ca sensor STIM1 or the Ca channel ORAI1. Currently, no treatment is available.

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