scholarly journals Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 2785
Author(s):  
Tomasz Boczek ◽  
Marta Sobolczyk ◽  
Joanna Mackiewicz ◽  
Malwina Lisek ◽  
Bozena Ferenc ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Secretory Pathway ◽  
Molecular Level ◽  
Calcium Signal ◽  
Pathological Changes ◽  
Calcium Pumps ◽  
Calcium Atpases ◽  
Mental Diseases ◽  
Altered Response ◽  
P Type

Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca2+ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca2+, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and secretory pathway Ca2+-ATPase (SPCA) are considered efficient line of defense against abnormal Ca2+ rises. However, their role is not limited only to Ca2+ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca2+-ATPases to neuropathology, with a special emphasis on mental diseases.

scholarly journals Two Distinctly Localized P-Type ATPases Collaborate to Maintain Organelle Homeostasis Required for Glycoprotein Processing and Quality Control

2002 ◽  
Vol 13 (11) ◽  
pp. 3955-3966 ◽  
Author(s):  
Shilpa Vashist ◽  
Christian G. Frank ◽  
Claude A. Jakob ◽  
Davis T.W. Ng
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Ion Homeostasis ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Coa Reductase ◽  
Protein Response ◽  
P Type ◽  
Er Homeostasis

Membrane transporter proteins are essential for the maintenance of cellular ion homeostasis. In the secretory pathway, the P-type ATPase family of transporters is found in every compartment and the plasma membrane. Here, we report the identification of COD1/SPF1(control of HMG-CoA reductase degradation/SPF1) through genetic strategies intended to uncover genes involved in protein maturation and endoplasmic reticulum (ER)-associated degradation (ERAD), a quality control pathway that rids misfolded proteins. Cod1p is a putative ER P-type ATPase whose expression is regulated by the unfolded protein response, a stress-inducible pathway used to monitor and maintain ER homeostasis. COD1 mutants activate the unfolded protein response and are defective in a variety of functions apart from ERAD, which further support a homeostatic role.COD1 mutants display phenotypes similar to strains lacking Pmr1p, a Ca2+/Mn2+pump that resides in the medial-Golgi. Because of its localization, the previously reported role of PMR1 in ERAD was somewhat enigmatic. A clue to their respective roles came from observations that the two genes are not generally required for ERAD. We show that the specificity is rooted in a requirement for both genes in protein-linked oligosaccharide trimming, a requisite ER modification in the degradation of some misfolded glycoproteins. Furthermore, Cod1p, like Pmr1p, is also needed for the outer chain modification of carbohydrates in the Golgi apparatus despite its ER localization. In strains deleted of both genes, these activities are nearly abolished. The presence of either protein alone, however, can support partial function for both compartments. Taken together, our results reveal an interdependent relationship between two P-type ATPases to maintain homeostasis of the organelles where they reside.

scholarly journals Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting

2014 ◽  
Vol 206 (5) ◽  
pp. 635-654 ◽  
Author(s):  
Christine Kienzle ◽  
Nirakar Basnet ◽  
Alvaro H. Crevenna ◽  
Gisela Beck ◽  
Bianca Habermann ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Nitrilotriacetic Acid ◽  
Calcium Atpase ◽  
Secretory Proteins ◽  
Dependent Manner ◽  
Agarose Beads ◽  
P Type ◽  
Golgi Network ◽  
Phosphorylation Domain ◽  
Cargo Sorting

The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132–amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1–dependent manner. This domain, coupled to nickel nitrilotriacetic acid (Ni-NTA) agarose beads, specifically recruited F-actin in the presence of CFL-1 and, when expressed in HeLa cells, inhibited Ca2+ entry into the TGN and secretory cargo sorting. Mutagenesis of four amino acids in SPCA1 that represent the CFL-1 binding site also affected Ca2+ import into the TGN and secretory cargo sorting. Altogether, our findings reveal the mechanism of CFL-1–dependent recruitment of actin to SPCA1 and the significance of this interaction for Ca2+ influx and secretory cargo sorting.

scholarly journals Pleiotropic Effects of the P5-Type ATPase SpfA on Stress Response Networks Contribute to Virulence in the Pathogenic Mold Aspergillus fumigatus

mBio ◽  
2021 ◽  
Author(s):  
José P. Guirao-Abad ◽  
Martin Weichert ◽  
Ginés Luengo-Gil ◽  
Sarah Sze Wah Wong ◽  
Vishukumar Aimanianda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Resistance ◽  
Secretory Pathway ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Gene Encoding ◽  
Content Type ◽  
Downstream Target ◽  
P Type ◽  
Er Homeostasis

The fungal UPR is an adaptive signaling pathway in the ER that buffers fluctuations in ER stress but also serves as a virulence regulatory hub in species of pathogenic fungi that rely on secretory pathway homeostasis for pathogenicity. This study demonstrates that the gene encoding the ER-localized P5-type ATPase SpfA is a downstream target of the UPR in the pathogenic mold A. fumigatus and that it works together with a second ER-localized P-type ATPase, SrcA, to support ER homeostasis, oxidative stress resistance, susceptibility to antifungal drugs, and virulence of A. fumigatus .

scholarly journals Requirement for Neo1p in Retrograde Transport from the Golgi Complex to the Endoplasmic Reticulum

2003 ◽  
Vol 14 (12) ◽  
pp. 4971-4983 ◽  
Author(s):  
Zhaolin Hua ◽  
Todd R. Graham
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Retrograde Transport ◽  
Transport Pathway ◽  
Transport Defect ◽  
Copii Vesicles ◽  
P Type ◽  
Adp Ribosylation Factor

Neo1p from Saccharomyces cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family. We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin. Here, we present evidence that epitope-tagged Neo1p localizes to the endoplasmic reticulum (ER) and Golgi complex and is required for a retrograde transport pathway between these organelles. Using conditional alleles of NEO1, we find that loss of Neo1p function causes cargo-specific defects in anterograde protein transport early in the secretory pathway and perturbs glycosylation in the Golgi complex. Rer1-GFP, a protein that cycles between the ER and Golgi complex in COPI and COPII vesicles, is mislocalized to the vacuole in neo1-ts at the nonpermissive temperature. These phenotypes suggest that the anterograde protein transport defect is a secondary consequence of a defect in a COPI-dependent retrograde pathway. We propose that loss of lipid asymmetry in the cis Golgi perturbs retrograde protein transport to the ER.

scholarly journals Candida albicansPmr1p, a Secretory Pathway P-type Ca2+/Mn2+-ATPase, Is Required for Glycosylation and Virulence

2005 ◽  
Vol 280 (24) ◽  
pp. 23408-23415 ◽  
Author(s):  
Steven Bates ◽  
Donna M. MacCallum ◽  
Gwyneth Bertram ◽  
Carol A. Munro ◽  
H. Bleddyn Hughes ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
P Type

scholarly journals Caspase activity in peripheral blood mononuclear cells (PBMC) of patients with depression and anxiety of different severity

2016 ◽  
Vol 62 (5) ◽  
pp. 588-592
Author(s):  
A.A. Yakovlev ◽  
T.A. Druzhkova ◽  
M.N. Grishkina ◽  
A.B. Guekht ◽  
N.V. Gulyaeva
Keyword(s):  
Mononuclear Cells ◽  
Brain Cells ◽  
Healthy Controls ◽  
Caspase Activity ◽  
Depression And Anxiety ◽  
Pathological Changes ◽  
Peripheral Blood Mononuclear ◽  
Mental Diseases ◽  
Blood Mononuclear Cells ◽  
Severe Anxiety

Though borderline psychiatric disorders (BPD) are quite common diseases, their pathogenesis remains obscure. Data from several groups and our previous results suggest that the pathological changes are typical not only for brain cells, but also for cells of the immune system. One of the evident illustrations of immune and nervous systems relationship in pathogenesis of mental diseases is the death of PBMC occurring in patients with depression. We have shown previously that activities of the caspases increase in some types of BPD. In this study, we have investigated caspase activities in PBMC of patients with BPD of different severity. It has been found that in severe depressive disorder activities of caspases were reduced either as compared to healthy controls or to patients with depression lesser severity. In contrast, in patients with severe anxiety activities of caspases were higher than in both control and patients with less severe forms of anxiety disorders. Thus, the study of caspase activity in PBMC makes it possible to differentiate between severe and mild forms of BPD.

scholarly journals New Insights Into Molecular Players Involved in Neurotransmitter Release

Physiology ◽  
2012 ◽  
Vol 27 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Pablo Ariel ◽  
Timothy A. Ryan
Keyword(s):  
Simple Model ◽  
Neurotransmitter Release ◽  
Molecular Level ◽  
Network Function

The strength of a synapse can profoundly influence network function. How this strength is set at the molecular level is a key question in neuroscience. Here, we review a simple model of neurotransmission that serves as a convenient framework to discuss recent studies on RIM and synaptotagmin.

scholarly journals Characterization of the Golgi Complex Cleared of Proteins in Transit and Examination of Calcium Uptake Activities

1997 ◽  
Vol 8 (10) ◽  
pp. 1911-1931 ◽  
Author(s):  
Randall S. Taylor ◽  
Steven M. Jones ◽  
Rolf H. Dahl ◽  
Mark H. Nordeen ◽  
Kathryn E. Howell
Keyword(s):  
Plasma Membrane ◽  
Golgi Complex ◽  
Secretory Pathway ◽  
Calcium Uptake ◽  
Rat Hepatocytes ◽  
Calcium Atpase ◽  
Endoplasmic Reticulum Calcium ◽  
Calcium Atpases ◽  
In Transit

To characterize endogenous molecules and activities of the Golgi complex, proteins in transit were >99% cleared from rat hepatocytes by using cycloheximide (CHX) treatment. The loss of proteins in transit resulted in condensation of the Golgi cisternae and stacks. Isolation of a stacked Golgi fraction is equally efficient with or without proteins in transit [control (CTL SGF1) and cycloheximide (CHX SGF1)]. Electron microscopy and morphometric analysis showed that >90% of the elements could be positively identified as Golgi stacks or cisternae. Biochemical analysis showed that the cis-, medial-, trans-, and TGN Golgi markers were enriched over the postnuclear supernatant 200- to 400-fold with and 400- to 700-fold without proteins in transit. To provide information on a mechanism for import of calcium required at the later stages of the secretory pathway, calcium uptake into CTL SGF1 and CHX SGF1 was examined. All calcium uptake into CTL SGF1 was dependent on a thapsigargin-resistant pump not resident to the Golgi complex and a thapsigargin-sensitive pump resident to the Golgi. Experiments using CHX SGF1 showed that the thapsigargin-resistant activity was a plasma membrane calcium ATPase isoform in transit to the plasma membrane and the thapsigargin-sensitive pump was a sarcoplasmic/endoplasmic reticulum calcium ATPase isoform. In vivo both of these calcium ATPases function to maintain millimolar levels of calcium within the Golgi lumen.

Effects of the putative P-type calcium channel blocker, R,R-(?)-daurisoline on neurotransmitter release

1995 ◽  
Vol 352 (6) ◽  
Author(s):  
PeterC. Waldmeier ◽  
Peter Wicki ◽  
Wolfgang Fr�stl ◽  
Helmut Bittiger ◽  
Jean-Jacques Feldtrauer
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Neurotransmitter Release ◽  
Channel Blocker ◽  
P Type
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