Vinu, M. | Search bioRxiv

bioRxiv2024

Loss of STIM1 and STIM2 in salivary glands disrupts ANO1 function but does not induce Sjogren's disease

Sjogrens disease (SjD) is an autoimmune disease characterized by xerostomia (dry mouth), lymphocytic infiltration into salivary glands and the presence of SSA and SSB autoantibodies. Xerostomia is caused by hypofunction of the salivary glands and has been involved in the development of SjD. Saliva production is regulated by parasympathetic input into the glands initiating intracellular Ca2+ signals that activate the store operated Ca2+ entry (SOCE) pathway eliciting sustained Ca2+ influx. SOCE is mediated by the STIM1 and STIM2 proteins and the ORAI1 Ca2+ channel. However, there are no studies on the effects of lack of STIM1/2 function in salivary acini in animal models and its impact on SjD. Here we report that male and female mice lacking Stim1 and Stim2 (Stim1/2K14Cre) in salivary glands showed reduced intracellular Ca2+ levels via SOCE in parotid acini and hyposalivate upon pilocarpine stimulation. Bulk RNASeq of the parotid glands of Stim1/2K14Cre mice showed a decrease in the expression of Stim1/2 but no other Ca2+ associated genes mediating saliva fluid secretion. SOCE was however functionally required for the activation of the Ca2+ activated chloride channel ANO1. Despite hyposalivation, ageing Stim1/2K14Cre mice showed no evidence of lymphocytic infiltration in the glands or elevated levels of SSA or SSB autoantibodies in the serum, which may be linked to the downregulation of the toll-like receptor 8 (Tlr8). By contrast, salivary gland biopsies of SjD patients showed increased STIM1 and TLR8 expression, and induction of SOCE in a salivary gland cell line increased the expression of TLR8. Our data demonstrate that SOCE is an important activator of ANO1 function and saliva fluid secretion in salivary glands. They also provide a novel link between SOCE and TLR8 signaling which may explain why loss of SOCE does not result in SjD.

physiology↗

bioRxiv2020

Beyond the greenhouse: coupling environmental and salt stress response reveals unexpected global transcriptional regulatory networks in Salicornia bigelovii

Soil salinity is an increasing threat to global food production systems. As such, there is a need for salt tolerant plant model systems in order to understand salt stress regulation and response. Salicornia bigelovii, a succulent obligatory halophyte, is one of the most salt tolerant plant species in the world. It possesses distinctive characteristics that make it a candidate plant model for studying salt stress regulation and tolerance, showing promise as an economical non-crop species that can be used for saline land remediation and for large-scale biofuel production. However, available S. bigelovii genomic and transcriptomic data are insufficient to reveal its molecular mechanism of salt tolerance. We performed transcriptome analysis of S. bigelovii flowers, roots, seeds and shoots tissues cultivated under desert conditions and irrigated with saline aquaculture effluent. We identified a unique set of tissue specific transcripts present in this non-model crop. A total of 66,943 transcripts (72.63%) were successfully annotated through the GO database with 18,321 transcripts (27.38%) having no matches to known transcripts. Excluding non-plant transcripts, differential expression analysis of 49,914 annotated transcripts revealed differentially expressed transcripts (DETs) between the four tissues and identified shoots and flowers as the most transcriptionally similar tissues relative to roots and seeds. The DETs between above and below ground tissues, with the exclusion of seeds, were primarily involved in osmotic regulation and ion transportation. We identified DETs between shoots and roots implicated in salt tolerance including SbSOS1, SbNHX, SbHKT6 upregulated in shoots relative to roots, while aquaporins (AQPs) were up regulated in roots. We also noted that DETs implicated in osmolyte regulation exhibit a different profile among shoots and roots. Our study provides the first report of a highly upregulated HKT6 from S. bigelovii shoot tissue. Furthermore, we identified two BADH transcripts with divergent sequence and tissue specific expression pattern. Overall, expression of the ion transport transcripts suggests Na+ accumulation in S. bigelovii shoots. Our data led to novel insights into transcriptional regulation across the four tissues and identified a core set of salt stress-related transcripts in S. bigelovii.

plant biology↗