TRPC1 contributes to the Ca2{+}-dependent regulation of adenylyl cyclases
Store-operated Ca2+ entry (SOCE) is mediated via specific plasma membrane channels in response to endoplasmic reticulum (ER) Ca2+ store depletion. This route of Ca2+ entry is central to the dynamic interplay between Ca2+ and cAMP signalling in regulating the activity of Ca2+-sensitive adenylyl cyclase isoforms (AC1/5/6/8). Two proteins have been identified as key components of SOCE: stromal interacting molecule 1 (STIM1) which senses ER Ca2+ store content and translocates to the plasma membrane upon store depletion, where it activates Orai1, the pore-forming component of the Ca2&#x...
Source: BJ Cell - August 18, 2014 Category: Biochemistry Authors: D Willoughby, H Ong, L Brito de Souza, S Wachten, I S. Ambudkar, D M.F. Cooper Tags: BJ Signal Source Type: research
Dynamitin Impacts Cell Surface Expression of Voltage-Gated Sodium Channel Nav1.5
This study strongly suggests that dynamitin is involved in the regulation of Nav1.5 cell surface density. (Source: BJ Cell)
Source: BJ Cell - August 4, 2014 Category: Biochemistry Authors: B Chatin, P Colombier, A Gamblin, M Allouis, F Le Bouffant Tags: BJ Cell Source Type: research
STIM1 regulates TRPC6 heteromultimerization and subcellular location
STIM1 (stromal interaction molecule-1) regulates store-operated channels in the plasma membrane but the regulation of TRPC heteromultimerization and location by STIM1 is poorly understood. STIM1 is a single transmembrane protein that communicates the filling state of the endoplasmic reticulum to store-operated channels. STIM1 has been reported to regulate the activity of all TRPC family members, except TRPC7. TRPC6 has been predominantly associated to second messenger-activated Ca2+ entry pathways. Here we report that STIM1 regulates the expression of TRPC6 in the plasma membrane and evokes translocation of this cha...
Source: BJ Cell - August 4, 2014 Category: Biochemistry Authors: L Albarran, N Dionisio, E Lopez, G M Salido, P C Redondo, J A. Rosado Tags: BJ Cell Source Type: research
PI4KII{alpha} phosphorylation by GSK3 directs vesicular trafficking to lysosomes
Glycogen synthase kinase 3 (GSK3) is essential for normal development and function of the central nervous system. It is especially important for regulating neurotransmission, although the downstream substrates mediating this function are not yet clear. Here, we report the lipid kinase phosphatidylinositol 4-kinase II alpha (PI4KIIa) is a novel substrate of GSK3 that regulates trafficking and cell surface expression of neurotransmitter receptors in neurons. GSK3 phosphorylates two distinct sites in the N-terminus of PI4KIIa (Ser5 and Ser47), promoting binding to the AP-3 complex for trafficking to the lysosome to be degrade...
Source: BJ Cell - August 1, 2014 Category: Biochemistry Authors: J W Robinson, I Leshchyns'ka, H Farghaian, W E Hughes, V Sytnyk, G G Neely, A R Cole Tags: BJ Signal Source Type: research
Serine/threonine kinase 16 and MAL2 regulate constitutive secretion of soluble cargo in hepatic cells
MAL2 (myelin and lymphocyte protein 2) is thought to regulate at least two steps in the hepatic apical transcytotic pathway. Because vesicle budding and delivery at each step are driven by complex machineries, we predicted that MAL2 participates in several large protein complexes with multiple binding partners. To identify novel MAL2 interactors, we performed split-ubiquitin yeast two-hybrid assays and identified serine-threonine kinase 16 (STK16) as a putative interactor which we verified morphologically and biochemically. Because STK16 is a Golgi-associated, constitutively active kinase implicated in regulating secretion...
Source: BJ Cell - August 1, 2014 Category: Biochemistry Authors: J G. In, A C. Striz, A Bernad, P L. Tuma Tags: BJ Cell Source Type: research
The small GTPase Rap1 promotes cell movement rather than stabilizes adhesion in epithelial cells responding to insulin-like growth factor I
TheRas-related GTPase Rap1 promotes cell adhesion and migration. Although the significance of Rap1 contribution to cell migration is increasingly being recognized, little is known about the biochemical mechanisms driving this process. Here, we discovered a previously unidentified regulatory role of insulin-like growth factor type I receptor (IGF-IR) in CRK SH3-binding guanine nucleotide exchange factor (C3G) -Rap1–fascin-actin axis promoting cell movement. We demonstrate that a burst of Rap1 activity, rather than presumed hyperactivation is imperative for the onset of cell movement. We show that while autophosphoryl...
Source: BJ Cell - July 16, 2014 Category: Biochemistry Authors: M A Guvakova, W S.Y. Lee, D K Furstenau, I Prabakaran, D C. Li, R Hung, N Kushnir Tags: BJ Cell Source Type: research
DNA-PKcs-interacting protein KIP binding to TRF2 is required for the maintenance of functional telomeres
Human telomeres associates with shelterin, a six-protein complex that protects chromosome ends from being recognized as sites of DNA damage. The shelterin subunit TRF2 protects telomeres by facilitating their organization into the protective capping structure. We have previously reported that DNA-PKcs-interacting protein KIP associates with telomerase through an interaction with hTERT. Here we identify KIP as a novel interacting partner of TRF2. KIP is able to interact with both TRF2 and DNA-PKcs at telomeres. Because KIP is required for the association between TRF2 and DNA-PKcs, the interplay of these three proteins may p...
Source: BJ Cell - July 11, 2014 Category: Biochemistry Authors: P Khadka, J Lee, S Baek, S Oh, I Chung Tags: BJ Cell Source Type: research
Histamine-induced Ca2{+} signaling is mediated by TRPM4 channels in human adipose-derived stem cells
Intracellular Ca2+ oscillations are frequently observed during stem cell differentiation and there is evidence that it may control adipogenesis. The Transient Receptor Potential Melastatin 4 channel (TRPM4) is a key regulator of Ca2+ signals in excitable and non-excitable cells. However, its role in human adipose-derived stem cells (hASCs), in particular during adipogenesis, is unknown. We investigated TRPM4 in hASCs and examined its impact on histamine-induced Ca2+ signaling and adipogenesis. By RT-PCR, we identified TRPM4 gene expression in hASCs and human adipose tissue. Electrophysiological recordi...
Source: BJ Cell - July 8, 2014 Category: Biochemistry Authors: T Doan Ngoc Tran, O Zolochevska, M L. Figueiredo, H Wang, L Yang, J M. Gimble, S Yao, H Cheng Tags: BJ Cell Source Type: research
Trypanosoma brucei eflornithine transporter AAT6 is a low affinity, low selective transporter for neutral amino acids
Amino acid transporters are crucial for parasite survival since the cellular metabolism of parasitic protozoa depends on the uptake of exogenous amino acids. Amino acid transporters are also of high pharmacological relevance because they may mediate uptake of toxic amino acid analogs. We now show that the eflornithine transporter AAT6 from Trypanosoma brucei mediates growth on neutral amino acids when expressed in Saccharomyces cerevisiae mutants. The transport was electrogenic and further analyzed in Xenopus laevis oocytes. Neutral amino acids, proline analogs, eflornithine and acivicin induced inward currents. For prolin...
Source: BJ Cell - July 2, 2014 Category: Biochemistry Authors: C Mathieu, A González Salgado, C Wirdnam, S Meier, M Suter Grotemeyer, E Inbar, P Mäser, D Zilberstein, E Sigel, P Bütikofer, D Rentsch Tags: BJ Disease Source Type: research
A systematic analysis reveals an essential role for high-affinity iron uptake system, hemolysin and CFEM domain-containing protein in iron homeostasis and virulence in Candida glabrata
Iron is an essential nutrient for all living organisms and human pathogens employ a battery of factors to scavenge iron from the high-affinity iron-binding host proteins. Here, we have elucidated, via a candidate gene approach, major iron acquisition and homeostatic mechanisms operational in an opportunistic human fungal pathogen Candida glabrata. Phenotypic, biochemical and molecular analysis of a set of 13 C. glabrata strains deleted for proteins, potentially implicated in iron metabolism, revealed that the high-affinity reductive iron uptake system is required for utilization of alternate carbon sources and for growth u...
Source: BJ Cell - July 2, 2014 Category: Biochemistry Authors: V Kumar Srivastava, K Jyothiraj Suneetha, R Kaur Tags: BJ Cell Source Type: research
Multiple ecto-nucleoside triphosphate diphosphohydrolases facilitate intracellular replication of Legionella pneumophila
In this study, we characterised the activity of a second eukaryotic-type NTPDase, Lpg0971, from L. pneumophila. We observed that recombinant Lpg0971 hydrolysed ATP only and exhibited divalent cation preference for manganese (II) ions. Similar to lpg1905, an lpg0971 mutant carrying the plasmid pMIP was attenuated in a mouse lung infection model and impaired for replication in human macrophages and amoebae. Increased trafficking of the Legionella containing vacuole (LCV) to a LAMP1 positive compartment was observed for both the lpg1905 and lpg0971 mutants carrying pMIP. Complementation with either lpg1905 or lpg0971 restored...
Source: BJ Cell - June 24, 2014 Category: Biochemistry Authors: P Riedmaier, F M Sansom, T Sofian, T Beddoe, R Schuelein, H J Newton, E L Hartland Tags: BJ Disease Source Type: research
A Single Element in the 3{'} UTR of the Apical Sodium-Dependent Bile Acid Transporter Controls both Stabilization and Destabilization of mRNA
mRNA stability appears to play a key role in the ontogenic regulation of the apical sodium dependent bile acid transporter (ASBT). The RNA binding proteins, Hu antigen R (HuR) and Tristetraprolin (TTP), stabilize and destabilize ASBT mRNA, respectively. Potential HuR binding sites were assessed by sequence analysis in the context of prior in vitro functional analyses of the rat ASBT 3’UTR. Wild type and mutant binding sites were investigated by gel shift analysis using IEC-6 cell extracts. The functional consequences of binding site mutations were assessed using two different hybrid reporter constructs linking the 3...
Source: BJ Cell - June 20, 2014 Category: Biochemistry Authors: D M Soler, A Ghosh, F Chen, B L Shneider Tags: BJ Gene Source Type: research
Cellular mechanisms underlying the increased disease severity seen for patients with long QT syndrome caused by compound mutations in KCNQ1
In conclusion, we have characterised the disease mechanisms for six LQT1 compound mutations and report that for four of these defective channel trafficking underlies the severe clinical phenotype. (Source: BJ Cell)
Source: BJ Cell - June 10, 2014 Category: Biochemistry Authors: S C Harmer, J S Mohal, A A Royal, W J McKenna, P D Lambiase, A Tinker Tags: BJ Disease Source Type: research
Identification of Protein Succination as a Novel Modification of Tubulin
Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). We demonstrate that both alpha (a) and beta (b) tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound dimethylfumarate (DMF, 500 μM) inhibited polymerization up to 35% and 59%, respectively. Using mass spectrometry we identified Cys347a, Cys376a, Cys12b and Cys303b as sites of succination in porcine ...
Source: BJ Cell - June 9, 2014 Category: Biochemistry Authors: G G Piroli, A M Manuel, M D Walla, M J Jepson, J WC Brock, M P Rajesh, R M Tanis, W E Cotham, N Frizzell Tags: BJ Cell Source Type: research
TM4SF5 suppression disturbs integrin {alpha}5-related signaling and muscle development in zebrafish
TM4SF5 is involved in epithelial-mesenchymal transition (EMT) for liver fibrosis and cancer metastasis. However, the function(s) of TM4SF5 during embryogenesis remains unknown. Here the effects of TM4SF5 on embryogenesis of zebrafish were investigated. tm4sf5 mRNA was expressed in posterior somites during somitogenesis and in whole myotome 1 dpf. tm4sf5 suppression impaired development of the trunk with aberrant morphology of muscle fibers and altered expression of integrin a5. The arrangement and adhesion of muscle cells were abnormally disorganized in tm4sf5 morphants with reduced muscle fiber masses, where integrin �...
Source: BJ Cell - June 4, 2014 Category: Biochemistry Authors: Y Choi, H Kim, J Kim, H Kim, M Kang, M Lee, J Ryu, H Song, S Nam, D Lee, K Kim, J Lee Tags: BJ Cell Source Type: research
