It has been suggested that syntaxin 5 (Syx5) participates in vesicular transport. We examined the effects of Syx5 down-regulation on the morphology of the Golgi apparatus and the transport of vesicles in mammalian cells. Knockdown of the Syx5 gene resulted in Golgi fragmentation without changing the level of endoplasmic reticulum (ER)-resident proteins, other Golgi-SNAREs (soluble N-ethylmaleimide-sensitive factorattachment protein receptors), and coatmer proteins. Strikingly, a major decrease in Syx5 expression barely affected the anterograde transport of vesicular stomatitis virus G (VSVG) protein to the plasma membrane. These results suggest that Syx5 is required for the maintenance of the Golgi structures but may not play a major role in the transport of vesicles carrying VSVG between the ER and the Golgi compartment.

The specific roles of syntaxin 5 (Syx 5) in the interaction with presenilin (PS) and the accumulation of b-amyloid precursor protein (bAPP), as well as the secretion of b-amyloid peptide (Ab peptide) were examined in NG108-15 cells. Syx 5, which localizes from the endoplasmic reticulum (ER) to the Golgi, bound to PS holoproteins, while the other Syxs studied did not. Among familial Alzheimer's disease (FAD)-linked PS mutants, PS1DE9, which lacks the endoproteolytic cleavage site, showed markedly decreased binding to Syx 5. The interaction domains in Syx 5 were mapped to the transmembrane region and to the cytoplasmic region containing the a-helical domains, which are distinct from the H3 (SNARE motif). Among all of the Syxs examined, only overexpression of Syx 5 resulted in the accumulation of bAPP in the ER to cis-Golgi compartment, an attenuation of the amount of the C-terminal fragment (APP-CTF) of bAPP, and a reduction in the secretion of Ab peptides. Furthermore, co-expression of Syx 5 with C99 resulted in an increase in APP-CTF and suppressed Ab secretion. Taken together, these results indicate that Syx 5 may play a specific role in the modulation of processing and/or trafficking of FAD-related proteins in neuronal cells by interaction with PS holoproteins in the early secretory compartment of neuronal cells.

In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of beta-amyloid precursor protein (betaAPP). Similar to Syx5, Syx5L bound to PS1 holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular betaAPP holoprotein, and did not inhibit amyloid beta peptide (Abeta) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of betaAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular betaAPP holoprotein and reduction in the secretion of Abeta. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of betaAPP in the early secretory compartment.

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Background The prevalence of acute renal infarction (ARI) in Japan remains unclear. We describe the clinical features and renal prognosis of ARI in Japanese patients. Methods This single-center, retrospective, observational study included 33 patients with newly diagnosed ARI (2009)(2010)(2011)(2012)(2013). Their clinical features and long-term renal outcomes were evaluated. Results The prevalence of ARI among emergency room patients was 0.013 %. The incidence of ARI among in-patients was 0.003 % (mean age 71.9 ± 13.4 years; men 63 %). Enhanced computed tomography or renal isotope scans were obtained to diagnose ARI. ARI involved the left kidney in 70 %, right kidney in 18 %, and both kidneys in 12 % of patients. Four cases had splenic infarction, and 70 % of patients had atrial fibrillation. We noted abdominal or flank pain in 66 %, fever ([37.6°C) in 36 %, and nausea/ vomiting in 6 % of patients. The white blood cell count, and levels of lactate dehydrogenase and C-reactive protein peaked at 2-4 days after onset. Acute kidney injury due to ARI occurred in 76 % of patients. The estimated glomerular filtration rate decreased to *70 % and recovered to *80 % of the original value after 1 year. The mortality rates were 9 and 15 % at 1 month and 1 year, respectively. Conclusions We determined the prevalence of ARI among emergency room patients, its incidence among inpatients, and short-term and long-term mortality. The majority of ARI cases were of cardiac origin, and the others were due to trauma or systemic thrombotic disease. Clinicians should recognize ARI as a fatal arterial thrombotic disease.