Dataset Information

Primary Active Ca²⁺ Transport Systems in Health and Disease.

ABSTRACT: Calcium ions (Ca²⁺) are prominent cell signaling effectors that regulate a wide variety of cellular processes. Among the different players in Ca²⁺ homeostasis, primary active Ca²⁺ transporters are responsible for keeping low basal Ca²⁺ levels in the cytosol while establishing steep Ca²⁺ gradients across intracellular membranes or the plasma membrane. This review summarizes our current knowledge on the three types of primary active Ca²⁺-ATPases: the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) pumps, the secretory pathway Ca²⁺- ATPase (SPCA) isoforms, and the plasma membrane Ca²⁺-ATPase (PMCA) Ca²⁺-transporters. We first discuss the Ca²⁺ transport mechanism of SERCA1a, which serves as a reference to describe the Ca²⁺ transport of other Ca²⁺ pumps. We further highlight the common and unique features of each isoform and review their structure-function relationship, expression pattern, regulatory mechanisms, and specific physiological roles. Finally, we discuss the increasing genetic and in vivo evidence that links the dysfunction of specific Ca²⁺-ATPase isoforms to a broad range of human pathologies, and highlight emerging therapeutic strategies that target Ca²⁺ pumps.

SUBMITTER: Chen J

PROVIDER: S-EPMC6996454 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Primary Active Ca2+ Transport Systems in Health and Disease.

Chen Jialin J Sitsel Aljona A Benoy Veronick V Sepúlveda M Rosario MR Vangheluwe Peter P

Cold Spring Harbor perspectives in biology 20200203 2

Calcium ions (Ca2+) are prominent cell signaling effectors that regulate a wide variety of cellular processes. Among the different players in Ca2+ homeostasis, primary active Ca2+ transporters are responsible for keeping low basal Ca2+ levels in the cytosol while establishing steep Ca2+ gradients across intracellular membranes or the plasma membrane. This review summarizes our current knowledge on the three types of primary active Ca2+< ...[more]

PMID: 31501194

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Project description:Cytosolic calcium (Ca2+) transients control key neural processes, including neurogenesis, migration, the polarization and growth of neurons, and the establishment and maintenance of synaptic connections. They are thus involved in the development and formation of the neural system. In this study, a publicly available whole transcriptome sequencing (RNA-Seq) dataset was used to examine the expression of genes coding for putative plasma membrane and organellar Ca2+-transporting proteins (channels, pumps, exchangers, and transporters) during the formation of the cerebral cortex in mice. Four ages were considered: embryonic days 11 (E11), 13 (E13), and 17 (E17), and post-natal day 1 (PN1). This transcriptomic profiling was also combined with live-cell Ca2+ imaging recordings to assess the presence of functional Ca2+ transport systems in E13 neurons. The most important Ca2+ routes of the cortical wall at the onset of corticogenesis (E11-E13) were TACAN, GluK5, nAChR β2, Cav3.1, Orai3, transient receptor potential cation channel subfamily M member 7 (TRPM7) non-mitochondrial Na+/Ca2+ exchanger 2 (NCX2), and the connexins CX43/CX45/CX37. Hence, transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1), transmembrane protein 165 (TMEM165), and Ca2+ "leak" channels are prominent intracellular Ca2+ pathways. The Ca2+ pumps sarco/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) and plasma membrane Ca2+ ATPase 1 (PMCA1) control the resting basal Ca2+ levels. At the end of neurogenesis (E17 and onward), a more numerous and diverse population of Ca2+ uptake systems was observed. In addition to the actors listed above, prominent Ca2+-conducting systems of the cortical wall emerged, including acid-sensing ion channel 1 (ASIC1), Orai2, P2X2, and GluN1. Altogether, this study provides a detailed view of the pattern of expression of the main actors participating in the import, export, and release of Ca2+. This work can serve as a framework for further functional and mechanistic studies on Ca2+ signaling during cerebral cortex formation.

Project description:ObjectiveTo understand how health systems are facilitating primary care redesign (PCR), examine the PCR initiatives taking place within systems, and identify barriers to this work.Study settingA purposive sample of 24 health systems in 4 states.Study designData were systematically reviewed to identify how system leaders define and implement initiatives to redesign primary care delivery and identify challenges. Researchers applied codes which were based on the theoretical PCR literature and created new codes to capture emerging themes. Investigators analyzed coded data then produced and applied a thematic analysis to examine how health systems facilitate PCR.Data collectionSemi-structured telephone interviews with 162 system executives and physician organization leaders from 24 systems.Principal findingsLeaders at all 24 health systems described initiatives to redesign the delivery of primary care, but many were in the early stages. Respondents described the use of centralized health system resources to facilitate PCR initiatives, such as regionalized care coordinators, and integrated electronic health records. Team-based care, population management, and care coordination were the most commonly described initiatives to transform primary care delivery. Respondents most often cited improving efficiency and enhancing clinician job satisfaction, as motivating factors for team-based care. Changes in payment and risk assumption as well as community needs were commonly cited motivators for population health management and care coordination. Return on investment and the slower than anticipated rate in moving from fee-for-service to value-based payment were noted by multiple respondents as challenges health systems face in redesigning primary care.ConclusionsGiven their expanding role in health care and the potential to leverage resources, health systems are promising entities to promote the advancement of PCR. Systems demonstrate interest and engagement in this work but face significant challenges in getting to scale until payment models are in alignment with these efforts.

Dataset Information

Primary Active Ca²⁺ Transport Systems in Health and Disease.

Publications

Primary Active Ca<sup>2+</sup> Transport Systems in Health and Disease.

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