Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized Caenorhabditis elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. We find that amino termini of human TMEM131 contain bacterial PapD chaperone-like domains, which recruit premature collagen monomers for proper assembly and secretion. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila, and humans

Comparative analysis of tissue expression and methylation reveal the crucial hypoxia genes in hypoxia resistant animals

Tibetan goat and Tibetan sheep are species peculiar to Qinghai-Tibetan Plateau which is the highest plateau in the world, and have high hypoxia resistance to the extremely bad environment. Unlike monogastrics, how the genes change responding to hypoxia in ruminants remains unclear. In the present study, three healthy animals of every breeds, including Tibetan sheep, Tibetan goat, Chuanzhong goat and Small-Tailed Han sheep were selected. The expression of factor inhibiting HIF 1 (FIH-1), hypoxia inducible factor 1α (HIF-1α), HIF-3α and erythropoietin (EPO) in various tissues, including heart, liver, lungs, kidney, muscle and brain, were investigated. EPO was observed highly expressed in all the tissues of Tibetan goats and Tibetan sheep compared with low-altitude animals respectively, implied that higher expression of EPO may give the explanation for the hypoxia resistance of plateau animals. Besides, we also cloned the promoters of FIH-1, HIF-1α, HIF-3α and EPO in goats and sheep, analyzed their core regions and CpG islands. Higher methylation rate was observed in HIF-1α, HIF-3α and EPO, while lower methylation rate hit on FIH-1. These data may be beneficial for revealing the response mechanism to hypoxia of plateau animals.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Diurnal Variation Characteristics of the Surface Sensible Heat Flux over the Tibetan Plateau

The characteristics of diurnal variation of the surface sensible heat flux (SH) over the Tibetan Plateau (TP) are comprehensively investigated by using the long-term dataset of integrated land–atmosphere interaction observations (2006–2016) on the TP. Results show that the diurnal variation of SH shows obvious seasonal variabilities in terms of amplitude, duration, and peak time. At the Muztagh Ata Westerly Observation and Research Station (MAWORS), the Ngari Desert Observation and Research Station (NADORS), and the Qomolangma Atmospheric and Environmental Observation and Research Station (QOMS), the SH diurnal amplitude is consistently the largest in spring, followed by summer and autumn, and the smallest in winter, with a peak at 15:00. However, for the Southeast Tibet Observation and Research Station (SETORS), the amplitude in winter is rather violent with the peak at 12:00. We find that positive SH at most stations has the longest duration from May to August. Moreover, the peak time fluctuates from month to month, even showing a shift at the QOMS before and after 2015, and the double-peak phenomenon of SH mainly occurs in spring and autumn. Additionally, magnitudes of calculated SH with the conventional heat transfer coefficient (CDH) of 0.004 are about 64–100% larger than those of directly observed SH at the QOMS and the Nam Co Monitoring and Research Station (NAMORS). We here additionally recommend a new CDH values of about 2.24 × 10−3 in spring and 2.78 × 10−3 in summer, respectively, to more accurately calculate the TP SH

The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics

TMEM39A encodes an evolutionarily conserved transmembrane protein and carries single-nucleotide polymorphisms associated with increased risk of major human autoimmune diseases, including multiple sclerosis. The exact cellular function of TMEM39A remains not well understood. Here, we report that TMEM-39, the sole Caenorhabditis elegans (C. elegans) ortholog of TMEM39A, regulates lysosome distribution and accumulation. Elimination of tmem-39 leads to lysosome tubularization and reduced lysosome mobility, as well as accumulation of the lysosome-associated membrane protein LMP-1. In mammalian cells, loss of TMEM39A leads to redistribution of lysosomes from the perinuclear region to cell periphery. Mechanistically, TMEM39A interacts with the dynein intermediate light chain DYNC1I2 to maintain proper lysosome distribution. Deficiency of tmem-39 or the DYNC1I2 homolog in C. elegans impairs mTOR signaling and activates the downstream TFEB-like transcription factor HLH-30. We propose evolutionarily conserved roles of TMEM39 family proteins in regulating lysosome distribution and lysosome-associated signaling, dysfunction of which in humans may underlie aspects of autoimmune diseases

Comparison of different grafting methods on the effect of 'Candidatus Liberibacter asiaticus' transmission

Grafting is a commonly used method for citrus propagation and transmitting 'Candidatus Liberibacter asiaticus' (CLas), the putative causing agent of citrus Huanglongbing (HLB). Optimization of the grafting inoculation methods facilitates the material preparation in HLB research. Citrus buds with CLas were grafted onto healthy sour tangerine (Citrus sunki Hort. ex Tanaka) seedlings by different methods such as top grafting ('T' grafting and 'V' grafting) and side grafting (abdominal grafting). Along with the symptom observation, titers of CLas in the leaves were detected by RT-qPCR monthly. The correlation between the growth status of buds or different grafting methods and the success rate of HLB transmission were analyzed. Our results suggest that sufficient DNA could be extracted to accurately detect the CLas from even only 0.0125 g leaf midrib or branch bark. The probability of CLas transmission was higher in plants inoculated with buds in better growth conditions. The success rate of 'T' grafting was significantly higher than that of side grafting and 'V' grafting. Additionally, in terms of HLB transmission efficiency, the two-bud grafting scheme was superior to the single-bud and three-bud grafting schemes. In conclusion, the grafting combinations with the highest HLB transmission efficiency were screened to provide a methodological reference for the practice or research of grafting to obtain plant material

The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.

Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How procollagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that the roles of TMEM-39 in collagen secretion and ER homeostasis are likely evolutionarily conserved

The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.

Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How procollagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that the roles of TMEM-39 in collagen secretion and ER homeostasis are likely evolutionarily conserved

The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.

Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How procollagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that the roles of TMEM-39 in collagen secretion and ER homeostasis are likely evolutionarily conserved