scholarly journals A pore-forming protein drives macropinocytosis to facilitate toad water maintaining

2021 ◽  
Author(s):  
Zhong Zhao ◽  
Zhihong Shi ◽  
Chenjun Ye ◽  
Yun Zhang

Maintaining water balance is a real challenge for amphibians in terrestrial environments. Our previous studies with toad Bombina maxima discovered a secretory aerolysin family pore-forming protein and trefoil factor complex βγ-CAT, which is assembled under tight regulation depending on environmental cues. Here we report an unexpected role for βγ-CAT in toad water maintaining. Deletion of toad skin secretions, in which βγ-CAT is a major component, increased animal mortality under hypertonic stress. βγ-CAT was constitutively expressed in toad osmoregulatory organs, which was inducible under the variation of osmotic conditions. The protein induced and participated in macropinocytosis in vivo and in vitro. During extracellular hyperosmosis, βγ-CAT stimulated macropinocytosis to facilitate water intake and enhanced exosomes release, which simultaneously regulated aquaporins distribution. Collectively, these findings uncovered that besides membrane integrated aquaporins, a secretory pore-forming protein can facilitate toad water maintaining via macropinocytosis induction and exocytosis modulation, especially in responses to osmotic stress.

2020 ◽  
Vol 15 (01) ◽  
pp. 1-34 ◽  
Author(s):  
Claudia Tanja Mierke

The classical migration modes, such as mesenchymal or amoeboid migration modes, are essentially determined by molecular, morphological or biochemical properties of the cells. These specific properties facilitate the cell migration and invasion through artificial extracellular matrices mimicking the environmental conditions of connective tissues. However, during the migration of cells through narrow extracellular matrix constrictions, the specific extracellular matrix environments can either support or impair the invasion of cells. Beyond the classical molecular or biochemical properties, the migration and invasion of cells depends on intracellular cell mechanical characteristics and extracellular matrix mechanical features. The switch between cell states, such as epithelial, mesenchymal or amoeboid states, seems to be mainly based on epigenetic changes and environmental cues that induce the reversible transition of cells toward another state and thereby promote a specific migration mode. However, the exact number of migration modes is not yet clear. Moreover, it is also unclear whether every individual cell, independent of the type, can undergo a transition between all different migration modes in general. A newer theory states that the transition from the jamming to unjamming phase of clustered cells enables cells to migrate as single cells through extracellular matrix confinements. This review will highlight the mechanical features of cells and their matrix environment that regulate and subsequently determine individual migration modes. It is discussed whether each migration mode in each cell type is detectable or whether some migration modes are limited to artificially engineered matrices in vitro and can therefore not or only rarely be detected in vivo. It is specifically pointed out how the intracellular architecture and its contribution to cellular stiffness or contractility favors the employment of a distinct migration mode. Finally, this review envisions a connection between mechanical properties of cells and matrices and the choice of a distinct migration mode in confined 3D microenvironments.


1995 ◽  
Vol 108 (4) ◽  
pp. A70
Author(s):  
R. Chinery ◽  
R. Playford ◽  
R. Poulsom ◽  
H.M. Cox

2005 ◽  
Vol 330 (4) ◽  
pp. 1027-1033 ◽  
Author(s):  
Jie Zhang ◽  
Yong Zhang ◽  
Shao-Gui Wan ◽  
Shuang-Shuang Wei ◽  
Wen-Hui Lee ◽  
...  

2005 ◽  
Vol 168 (3) ◽  
pp. 401-414 ◽  
Author(s):  
Tracy J. LaGrassa ◽  
Christian Ungermann

The regulation of cellular membrane flux is poorly understood. Yeast respond to hypertonic stress by fragmentation of the normally large, low copy vacuole. We used this phenomenon as the basis for an in vivo screen to identify regulators of vacuole membrane dynamics. We report here that maintenance of the fragmented phenotype requires the vacuolar casein kinase I Yck3: when Yck3 is absent, salt-stressed vacuoles undergo fission, but reassemble in a SNARE-dependent manner, suggesting that vacuole fusion is disregulated. Accordingly, when Yck3 is deleted, in vitro vacuole fusion is increased, and Yck3 overexpression blocks fusion. Morphological and functional studies show that Yck3 modulates the Rab/homotypic fusion and vacuole protein sorting complex (HOPS)-dependent tethering stage of vacuole fusion. Intriguingly, Yck3 mediates phosphorylation of the HOPS subunit Vps41, a bi-functional protein involved in both budding and fusion during vacuole biogenesis. Because Yck3 also promotes efficient vacuole inheritance, we propose that tethering complex phosphorylation is a part of a general, switch-like mechanism for driving changes in organelle architecture.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Brittany N. Ross ◽  
Joseph D. Thiriot ◽  
Shane M. Wilson ◽  
Alfredo G. Torres

Abstract Burkholderia pseudomallei (Bpm) is a bacterial pathogen that causes Melioidosis, a disease with up to 40% mortality and an infection relapse of 15–23% despite antibiotic treatment. Ineffective clearance of Bpm by antibiotics is believed to be due to persistence, a hibernation-like survival mechanism modulated, in part, by toxin–antitoxin systems (TAS). Several organisms possess a repertoire of TASs but defining environmental cues eliciting their activity is hindered by laborious in vitro experiments, especially when there are many toxins with redundant function. Here, we identified which of 103 proteins in Bpm that share features found in toxins of the TAS and repurposed transcriptional data to identify which ones play a role in surviving intracellular host defenses. Putative toxins with the strongest transcriptional response were found to have low conservation between Bpm strains, while toxins that were constitutively expressed were highly conserved. Further examination of highly conserved toxins BPSS0899, BPSS1321, and BPSL1494 showed that they were functional, and their mutation led to reduce survival within macrophages and reduced in vivo persistence-associated pathology (abscesses) during treatment, but did not affect macrophages persistence. These findings highlight the utility of a data-driven approach to select putative toxins and suggests a selective role for some TAS in host survival.


Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2361-2371
Author(s):  
A.K. Hall ◽  
S.E. MacPhedran

Adult rat sympathetic neurons can possess specific neuropeptides utilized as cotransmitters along with norepinephrine, but the factors that regulate their expression remain unknown. 60% of adult rat superior cervical ganglion (SCG) neurons express neuropeptide Y (NPY) in vivo. To determine whether the restricted expression was an intrinsic property of sympathetic ganglia, we examined if embryonic sympathetic precursors gave rise to NPY immunoreactive (-IR) neurons in vitro. After one week in culture, 60% of neurons derived from the E14.5 rat SCG were NPY-IR. Thus, ganglia isolated before peripheral target contact or preganglionic innervation were capable of regulating NPY expression both in the number of neurons with NPY and in the developmental timing of NPY expression. To determine if the restricted expression of NPY was a reflection of neuroblasts committed to an NPY fate, SCG precursors were labeled with a replication incompetent retrovirus carrying lacZ, and NPY expression in lacZ-labeled clones examined after one week. Two thirds of neuronal clones obtained were uniformly NPY-IR; that is, all neurons in a clone either possessed or lacked NPY. One-third of the neuronal clones were mixed and contained both neurons with and without NPY. We provide a novel demonstration that both lineage and environmental cues contribute to neuropeptide phenotype.


2017 ◽  
Vol 139 (2) ◽  
Author(s):  
Brett S. Klosterhoff ◽  
Melissa Tsang ◽  
Didi She ◽  
Keat Ghee Ong ◽  
Mark G. Allen ◽  
...  

The translation of many tissue engineering/regenerative medicine (TE/RM) therapies that demonstrate promise in vitro are delayed or abandoned due to reduced and inconsistent efficacy when implemented in more complex and clinically relevant preclinical in vivo models. Determining mechanistic reasons for impaired treatment efficacy is challenging after a regenerative therapy is implanted due to technical limitations in longitudinally measuring the progression of key environmental cues in vivo. The ability to acquire real-time measurements of environmental parameters of interest including strain, pressure, pH, temperature, oxygen tension, and specific biomarkers within the regenerative niche in situ would significantly enhance the information available to tissue engineers to monitor and evaluate mechanisms of functional healing or lack thereof. Continued advancements in material and fabrication technologies utilized by microelectromechanical systems (MEMSs) and the unique physical characteristics of passive magnetoelastic sensor platforms have created an opportunity to implant small, flexible, low-power sensors into preclinical in vivo models, and quantitatively measure environmental cues throughout healing. In this perspective article, we discuss the need for longitudinal measurements in TE/RM research, technical progress in MEMS and magnetoelastic approaches to implantable sensors, the potential application of implantable sensors to benefit preclinical TE/RM research, and the future directions of collaborative efforts at the intersection of these two important fields.


Author(s):  
A.J. Lawrence

An in vitro bioassay has been developed which shows that oogenesis in Harmothoe imbricata is controlled by a gonadotrophic hormone which promotes egg protein synthesis in developing oocytes. A similar endocrine control mechanism is found in Eulalia viridis and analysis of in vivo assays indicate that the hormone acts as a transducer between the environment and the gamete. The timing of gametogenesis is controlled by environmental cues in both species and may be affected by predicted global climate change. With the development of these sensitive hormone assays it is possible to test the impact of climate change on both species, providing a possible early warning system for global warming and potential bio-indicators of climate change. Harmothoe imbricata is likely to be the more sensitive indicator species.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 761
Author(s):  
Dahee Yeo ◽  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee

This study was designed to determine whether α-humulene, a major constituent in many plants used in fragrances, has a protective role against gastric injury in vivo and in vitro. A rat model of hydrochloric acid (HCl)/ethanol-induced gastritis and human mast cells (HMC-1) were used to investigate the mucosal protective effect of α-humulene. α-Humulene significantly inhibited gastric lesions in HCl/ethanol-induced acute gastritis and decreased gastric acid secretion pyloric ligation-induced gastric ulcers in vivo. In addition, α-humulene reduced the amount of reactive oxygen species and malondialdehyde through upregulation of prostaglandin E2 (PGE2) and superoxide dismutase (SOD). In HMC-1 cells, α-humulene decreased intracellular calcium and increased intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in low histamine levels. α-Humulene also reduced the expression levels of cytokine genes such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF) by downregulating nuclear factor-κB (NF-κB) nuclear translocation. Finally, α-humulene upregulated the expression levels of mucin 5AC (Muc5ac), Muc6, trefoil factor 1 (Tff1), trefoil factor 2 (Tff2), and polymeric immunoglobulin receptor (pigr). α-Humulene may attenuate HCl/ethanol-induced gastritis by inhibiting histamine release and NF-κB activation and stimulating antioxidants and mucosal protective factors, particularly Muc5ac and Muc6. Therefore, these data suggest that α-humulene is a potential drug candidate for the treatment of stress-induced or alcoholic gastritis.


Sign in / Sign up

Export Citation Format

Share Document