Phosphorylation cycling of Annexin A2 Tyr23 is critical for calcium-regulated exocytosis in neuroendocrine cells.

07:00 EST 2nd January 2019 | BioPortfolio

Summary of "Phosphorylation cycling of Annexin A2 Tyr23 is critical for calcium-regulated exocytosis in neuroendocrine cells."

Annexin A2 (AnxA2) is a calcium and lipid binding protein involved in neuroendocrine secretion. We have previously demonstrated that AnxA2 participates in the formation and/or stabilization of lipid microdomains required for structural and spatial organization of the exocytotic machinery in chromaffin cells. However, the regulation of AnxA2 is not fully understood. Numerous phosphorylation sites have been identified in the amino-terminal domain of AnxA2. Phosphorylation of Ser25 and Tyr23 are well established and confirmed to be functionally significant. In particular, phosphorylation of Tyr23 by the tyrosine kinase pp60Src reduces the binding of AnxA2 to both actin filaments and the plasma membrane, two major actors of exocytosis, thus, we examined whether AnxA2 was phosphorylated on Tyr23 during exocytosis. Using immunolabelling and a biochemical approach, we found that nicotine stimulation triggered the phosphorylation of Anx A2 on Tyr23. The expression of two AnxA2 mutants carrying phosphorylation deficient (Y23A) or phosphomimetic (Y23E) mutations reduced the number exocytotic sites. Furthermore, expression of AnxA2-Y23A inhibited the formation of lipid microdomains, whereas the expression of AnxA2-Y23E altered actin filaments associated with docked granules. These results suggest that phosphorylation/dephosphorylation switch at Tyr23 in AnxA2 is critical for calcium-regulated exocytosis in neuroendocrine cells. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.


Journal Details

This article was published in the following journal.

Name: Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596


DeepDyve research library

PubMed Articles [12470 Associated PubMed Articles listed on BioPortfolio]

Cyclophilin D Phosphorylation is Critical for Mitochondrial Calcium Uniporter Regulated Permeability Transition Pore Sensitivity.

Calcium homeostasis is critical for the cell fate, physiological calcium levels are important for cellular metabolism; however calcium overload in mitochondrial matrix can trigger mitochondrial permea...

Annexin A2 expression and partners during epithelial cell differentiation.

The members of the annexin family of calcium- and phospholipid-binding proteins participate in different cellular processes. Annexin A2 binds to S100A10 forming a functional heterotetrameric protein t...

The SNAP-25 protein family.

SNARE-complexes drive the fusion of membrane-bound vesicles with target membranes or with each other (homotypic fusion). The SNARE-proteins are subdivided into Q, Q, Q and R-SNAREs depending on their ...

Grab recruitment by Rab27A-Rabphilin3a triggers Rab3A activation in human sperm exocytosis.

Sperm must undergo the regulated exocytosis of its dense core granule (the acrosome reaction, AR) to fertilize the egg. We have previously described that Rabs3 and 27 are organized in a RabGEF cascade...

Symmetrical Organization of Proteins Under Docked Synaptic-Vesicles.

During calcium-regulated exocytosis, the constitutive fusion machinery is 'clamped' in a partially-assembled state until synchronously released by calcium. The protein machinery involved in this proce...

Clinical Trials [2830 Associated Clinical Trials listed on BioPortfolio]

CYCLE: A Randomized Clinical Trial of Early In-bed Cycling for Mechanically Ventilated Patients

Patients who survive critical illness usually experience long-lasting physical and psychological impairments, which are often debilitating. Rehabilitation interventions started in the ICU ...

99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques

The aim of this trial will be to test and validate the value of scintigraphy with injection of 99mTc-Annexin-V-128 for the detection of complicated carotid plaques

Fetuin-A Phosphorylation Status in Insulin Resistance and Metabolic Syndrome

Fetuin-A has been identified as a novel physiological regulator of insulin action in vitro, in intact cells and in vivo in animals. Previous research has shown that circulating levels of f...

Annexin Imaging in Dissection of the Descending Aorta

The relationship between the presence of a partial thrombus and aortic dilation after type B dissection has recently been reported. The originality lies in the idea of imaging thrombus act...

Effects of Functional Electrical Stimulation Cycling Versus Cycling Only on Walking and Quality of Life in MS

This study will seek to determine the benefits that FES-LE cycling has over cycling alone on walking performance and quality of life in people with multiple sclerosis.

Medical and Biotech [MESH] Definitions

An annexin family member that plays a role in MEMBRANE FUSION and signaling via VOLTAGE-DEPENDENT CALCIUM CHANNELS.

A member of the annexin family that is a substrate for a tyrosine kinase, ONCOGENE PROTEIN PP60(V-SRC). Annexin A2 occurs as a 36-KDa monomer and in a 90-KDa complex containing two subunits of annexin A2 and two subunits of S100 FAMILY PROTEIN P11. The monomeric form of annexin A2 was formerly referred to as calpactin I heavy chain.

A set of opposing, nonequilibrium reactions catalyzed by different enzymes which act simultaneously, with at least one of the reactions driven by ATP hydrolysis. The results of the cycle are that ATP energy is depleted, heat is produced and no net substrate-to-product conversion is achieved. Examples of substrate cycling are cycling of gluconeogenesis and glycolysis pathways and cycling of the triglycerides and fatty acid pathways. Rates of substrate cycling may be increased many-fold in association with hypermetabolic states resulting from severe burns, cold exposure, hyperthyroidism, or acute exercise.

A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

A monomeric calcium-calmodulin-dependent protein kinase subtype that specifically phosphorylates PEPTIDE ELONGATION FACTOR 2. The enzyme lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE, however it is regulated by phosphorylation by PROTEIN KINASE A and through intramolecular autophosphorylation.

Quick Search


DeepDyve research library

Relevant Topic

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article