N-glycosylation critically regulates function of oxalate transporter SLC26A6
The brush border Cl–-oxalate exchanger SLC26A6 plays an essential role in mediating intestinal secretion of oxalate and is crucial for the maintenance of oxalate homeostasis and the prevention of hyperoxaluria and calcium oxalate nephrolithiasis. Previous in vitro studies have suggested that SLC26A6 is heavily N-glycosylated. N-linked glycosylation is known to critically affect folding, trafficking, and function in a wide variety of integral membrane proteins and could therefore potentially have a critical impact on SLC26A6 function and subsequent oxalate homeostasis. Through a series of enzymatic deglycosylation stu...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Thomson, R. B., Thomson, C. L., Aronson, P. S. Tags: ARTICLES Source Type: research
Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion
Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 overexpression (C...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Kassan, A., Pham, U., Nguyen, Q., Reichelt, M. E., Cho, E., Patel, P. M., Roth, D. M., Head, B. P., Patel, H. H. Tags: ARTICLES Source Type: research
Mechanotransduction of the endothelial glycocalyx mediates nitric oxide production through activation of TRP channels
The endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the vascular endothelium, serving critical functions in the mechanotransduction of blood flow-induced forces. One of the most important protective functions of the ESG is to mediate the production of nitric oxide (NO) in response to blood flow. However, the detailed mechanism underlying ESG's mechanotransduction of the production of NO has not been completely identified. Herein, using the cultured rat brain microvascular endothelial cells (bEnd.3) as a model system, we have implemented a combined atomic force and fluorescence microscopy approach...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Dragovich, M. A., Chester, D., Fu, B. M., Wu, C., Xu, Y., Goligorsky, M. S., Zhang, X. F. Tags: CALL FOR PAPERS Source Type: research
Deficiency of the intermediate filament synemin reduces bone mass in vivo
While the type IV intermediate filament protein, synemin, has been shown to play a role in striated muscle and neuronal tissue, its presence and function have not been described in skeletal tissue. Here, we report that genetic ablation of synemin in 14-wk-old male mice results in osteopenia that includes a more than 2-fold reduction in the trabecular bone fraction in the distal femur and a reduction in the cross-sectional area at the femoral middiaphysis due to an attendant reduction in both the periosteal and endosteal perimeter. Analysis of serum markers of bone formation and static histomorphometry revealed a statistica...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Moorer, M. C., Buo, A. M., Garcia-Pelagio, K. P., Stains, J. P., Bloch, R. J. Tags: RAPID REPORTS Source Type: research
The cytoskeleton meets the skeleton. Focus on "Deficiency of the intermediate filament synemin reduces bone mass in vivo"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Skalli, O. Tags: EDITORIAL FOCUS Source Type: research
RACK1 is required for adipogenesis
Adipose tissue plays a critical role in metabolic diseases and the maintenance of energy homeostasis. RACK1 has been identified as an adaptor protein involved in multiple intracellular signal transduction pathways and diseases. However, whether it regulates adipogenesis remains unknown. Here, we reported that RACK1 is expressed in 3T3-L1 cells and murine white adipose tissue and that RACK1 knockdown by shRNA profoundly suppressed adipogenesis by reducing the expression of PPAR- and C/EBP-β. Depletion of RACK1 increased β-catenin protein levels and activated Wnt signaling. Furthermore, RACK1 knockdown also suppres...
Source: AJP: Cell Physiology - November 10, 2016 Category: Cytology Authors: Kong, Q., Gao, L., Niu, Y., Gongpan, P., Xu, Y., Li, Y., Xiong, W. Tags: RAPID REPORTS Source Type: research
Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants
Congenital hereditary endothelial dystrophy (CHED), Harboyan syndrome (CHED with progressive sensorineural deafness), and potentially a subset of individuals with late-onset Fuchs' endothelial corneal dystrophy are caused by mutations in the SLC4A11 gene that results in corneal endothelial cell abnormalities. Originally classified as a borate transporter, the function of SLC4A11 as a transport protein remains poorly understood. Elucidating the transport function(s) of SLC4A11 is needed to better understand how its loss results in the aforementioned posterior corneal dystrophic disease processes. Quantitative PCR experiment...
Source: AJP: Cell Physiology - November 10, 2016 Category: Cytology Authors: Kao, L., Azimov, R., Shao, X. M., Frausto, R. F., Abuladze, N., Newman, D., Aldave, A. J., Kurtz, I. Tags: ARTICLES Source Type: research
Ca2+-activated Cl- channel currents in mammary secretory cells from lactating mouse
The Cl– secretion via Ca2+-activated Cl– channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl– and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed membrane current in MS cells that were freshly isolated from lactating mice using whole cell patch-clamp techniques. In MS cells, we detected CaCC current that exhibited the following ch...
Source: AJP: Cell Physiology - November 10, 2016 Category: Cytology Authors: Kamikawa, A., Ichii, O., Sakazaki, J., Ishikawa, T. Tags: ARTICLES Source Type: research
Making isotonic milk. Focus on "Ca2+-activated Cl- channel currents in mammary secretory cells from lactating mouse"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - November 10, 2016 Category: Cytology Authors: Schultz, B. D. Tags: EDITORIAL FOCUS Source Type: research
Tuning the proteasome to brighten the end of the journey
Degradation by the proteasome is the fate for a large portion of cellular proteins, and it plays a major role in maintaining protein homeostasis, as well as in regulating many cellular processes like cell cycle progression. A decrease in proteasome activity has been linked to aging and several age-related neurodegenerative pathologies and highlights the importance of the ubiquitin proteasome system regulation. While the proteasome has been traditionally viewed as a constitutive element of proteolysis, major studies have highlighted how different regulatory mechanisms can impact its activity. Importantly, alterations of pro...
Source: AJP: Cell Physiology - November 10, 2016 Category: Cytology Authors: Mayor, T., Sharon, M., Glickman, M. H. Tags: THEMES Source Type: research
Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl- secretion in human colonic T84 cells
This study establishes the complexity of CDCA signaling in the colonic epithelium and shows the contribution of EGFR, EPAC, and Ca2+ in CDCA-induced activation of CFTR-dependent Cl– secretion. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Domingue, J. C., Ao, M., Sarathy, J., Rao, M. C. Tags: ARTICLES Source Type: research
Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells
Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal tubule stimulates Na+/H+ exchanger isoform 3 (NHE3) activity through multiple signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3 regulation are not well established. We therefore tested the hypothesis that ANG II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3 activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in o...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Crajoinas, R. O., Polidoro, J. Z., Carneiro de Morais, C. P. A., Castelo-Branco, R. C., Girardi, A. C. C. Tags: ARTICLES Source Type: research
SM22{alpha} inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs
We previously demonstrated that smooth muscle (SM) 22α promotes the migration activity in contractile vascular smooth muscle cells (VSMCs). Based on the varied functions exhibited by SM22α in different VSMC phenotypes, we investigated the effect of SM22α on VSMC migration under pathological conditions. The results demonstrated that SM22α overexpression in synthetic VSMCs inhibited platelet-derived growth factor (PDGF)-BB-induced cell lamellipodium formation and migration, which was different from its action in contractile cells. The results indicated two distinct mechanisms underlying inhibition of ...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Lv, P., Zhang, F., Yin, Y.-J., Wang, Y.-C., Gao, M., Xie, X.-L., Zhao, L.-L., Dong, L.-H., Lin, Y.-L., Shu, Y.-N., Zhang, D.-D., Liu, G.-X., Han, M. Tags: CALL FOR PAPERS Source Type: research
Malignant hyperthermia-associated mutations in the S2-S3 cytoplasmic loop of type 1 ryanodine receptor calcium channel impair calcium-dependent inactivation
Channel activities of skeletal muscle ryanodine receptor (RyR1) are activated by micromolar Ca2+ and inactivated by higher (~1 mM) Ca2+. To gain insight into a mechanism underlying Ca2+-dependent inactivation of RyR1 and its relationship with skeletal muscle diseases, we constructed nine recombinant RyR1 mutants carrying malignant hyperthermia or centronuclear myopathy-associated mutations and determined RyR1 channel activities by [3H]ryanodine binding assay. These mutations are localized in or near the RyR1 domains which are responsible for Ca2+-dependent inactivation of RyR1. Four RyR1 mutations (F4732D, G4733E, R4736W, ...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Gomez, A. C., Holford, T. W., Yamaguchi, N. Tags: ARTICLES Source Type: research
Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies
SLC4A11, a member of the SLC4 family of bicarbonate transporters, is a widely expressed integral membrane protein, abundant in kidney and cornea. Mutations of SLC4A11 cause some cases of the blinding corneal dystrophies, congenital hereditary endothelial dystrophy, and Fuchs endothelial corneal dystrophy. These diseases are marked by fluid accumulation in the corneal stroma, secondary to defective fluid reabsorption by the corneal endothelium. The role of SLC4A11 in these corneal dystrophies is not firmly established, as SLC4A11 function remains unclear. To clarify the normal function(s) of SLC4A11, we characterized the pr...
Source: AJP: Cell Physiology - October 31, 2016 Category: Cytology Authors: Loganathan, S. K., Schneider, H.-P., Morgan, P. E., Deitmer, J. W., Casey, J. R. Tags: ARTICLES Source Type: research
