Aberrant localization of fusion receptors involved in regulated exocytosis in salivary glands of Sjögren’s syndrome patients is linked to ectopic mucin secretion

Sjögren's syndrome and the epithelial target: A comprehensive review

“…Also, STX3 presence increased in the cytoplasm and the basolateral plasma membrane [1], presumably, favoring granulee granule fusion, as was observed in previous studies [100]. Additionally, also apico-basal redistribution of STX4, SNAP-23 and VAMP8 is observed in SS-patient acinar cells [1]. These redistributions were similar those observed for claudin 3, ezrin and Rab3D [44,45,132].…”

“…On the other hand, for STX3, an SNARE protein involved in granuleegranule fusion, a significant increase in protein levels was detected in SSpatients. Also, STX3 presence increased in the cytoplasm and the basolateral plasma membrane [1], presumably, favoring granulee granule fusion, as was observed in previous studies [100]. Additionally, also apico-basal redistribution of STX4, SNAP-23 and VAMP8 is observed in SS-patient acinar cells [1].…”

“…Interestingly, in the absence of secretory exogenous stimulation, atypical STX4-RAB3D colocalization was observed in the basal and lateral plasma membrane domains for SS-patients [1]. Additionally, we observed an increase in the formation of SNARE complexes for VAMP8, STX4 and SNAP-23 under basal conditions.…”

“…Increased functional SNARE complexes with anomalous localization likely represent the cause of ectopic exocytotic processes, such as aberrant secretion of mucins from acinar cells towards the ECM, as was observed for MUC7 and MUC5B (Fig. 5) [1]. In this context, it is intriguing to speculate that such aberrantly secreted mucins may promote inflammation and disease progression.…”

“…4) [132]. Interestingly, Rab3D redistribution was accompanied by mislocalization of ezrin from the apical to basolateral membrane, loss of nuclear polarity, increased volume of the Golgi complex, MUC7 accumulation in the cytosol [132] and STX4 localization to the basolateral plasma membrane of serous acini [1]. These results are indicative of drastic alterations in the normal destination of the secretory granules to the apical plasma membrane.…”