Nuclear pore disassembly from endoplasmic reticulum membranes promotes Ca2+ signalling competency
Michael J Boulware1, Jonathan S Marchant
1Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
The Journal of Physiology
|May 3, 2008
Summary
Annulate lamellae (AL) regulate calcium signaling by suppressing activity via nuclear pore complexes (NPCs). Their disassembly allows localized calcium signaling, enabling rapid cellular function changes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Endoplasmic reticulum (ER) regulates cytosolic calcium (Ca2+) via pumps, buffers, and channels.
- Heterogeneity in ER Ca2+ fluxes is known, but regulation within proximal ER regions remains unclear.
Purpose of the Study:
- Investigate the in vivo dynamics of annulate lamellae (AL), an ER subdomain.
- Determine how nuclear pore complexes (NPCs) within AL affect local Ca2+ signaling.
Main Methods:
- Studied in vivo dynamics of annulate lamellae (AL).
- Investigated the role of nuclear pore complexes (NPCs) in Ca2+ signaling within AL.
Main Results:
- NPCs within AL suppress local Ca2+ signaling activity.
- Heterogeneous dissociation of nucleoporins from NPCs in AL relieves suppression.
- NPC-denuded ER domains become competent for Ca2+ signaling.
Conclusions:
- AL function as a mechanism for reversible attenuation of resident protein activity.
- Regulated AL disassembly via a kinase/phosphatase cycle enables rapid cellular physiological transitions.
Related Concept Videos
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:42Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
01:46Nuclear Localization Signals and Import
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
01:42Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...