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The annexins are a family of proteins that bind anionic phospholipid surfaces in a Ca(2+)-dependent manner (general reviews include Raynal & Pollard 1994, Swairjo & Seaton 1994, Seaton 1996, Mollenhauer, 1997). Due to this functional property, individual annexins have been discovered independently by numerous laboratories with diverse experimental goals. Ca2+ characteristically causes the annexins to shift from a soluble to membrane associated state. This shift is believed to be the mechanism that underlies annexin cellular function.

Annexins are a unique family of membrane-associated, Ca2+ and phospholipid-binding proteins found in various tissues. Among the 12 isoforms, Annexin II, V and VI exist in heart tissue in the highest amounts. Annexin VI has been shown to affect intracellular Ca2+ cycling and contractility in isolated cardiomyocytes. Annexin V is present in both cardiomyocytes and non-myocyte cell types in the heart and may play a role in the regulation of cellular ion fluxes, organization and secretion, while the cardiac effects of annexin II are unclear. To identify changes in annexin II, V and VI isoforms that might occur in human heart failure, we measured mRNA and protein levels of these three annexins in transplanted left ventricular tissue of 12 patients with end-stage congestive heart failure due to coronary artery disease (CAD, n=6) or idiopathic dilated cardiomyopathy (DCM, n=6) who underwent cardiac transplantation. Normal heart tissue (C, n=6) was used as a control. Northern blot analyses showed a significant decrease (61%) in annexin VI mRNA levels in heart failure patients compared with controls (1.08+/-0.16 v 2.79+/-0.20 A.U.C. unit, determined by laser densitometry, mean+/-s.e.). In contrast, we found a 67% increase (2. 32+/-0.27 v 3.88+/-0.29) in annexin II mRNA levels and a two-fold increase (1.00+/-0.24 v 2.21+/-0.29) in annexin V mRNA levels in cardiomyopathic hearts as compared to normal hearts. Western blot analyses demonstrated a corresponding decrease (46.1%) in annexin VI protein levels in the heart failure group as compared to controls (2. 63+/-0.22 v 4.88+/-0.52), while annexin II protein levels showed a significant 40.7% increase in patients with heart failure compared to those in normal hearts (5.08+/-0.67 v 3.61+/-0.32). Annexin V protein levels were also significantly increased (45%) in heart failure patients compared with normal (2.14+/-0.19 v 1.48+/-0.11). No difference in either annexins II, V or VI mRNA and protein levels were found between CAD and DCM patients. We conclude that human end-stage heart failure is associated with a down regulation of annexin VI and up regulation of annexin II and V proteins. Coordinate changes were observed in steady-state mRNA levels. These results suggest that these annexin isoforms may contribute to the regulation of intracellular Ca2+ homeostasis in the cardiomyopathic heart., (Copyright 1998 Academic Press Limited)

The annexins are a family of Ca(2+)-dependent phospholipid-binding proteins. In the present study, the spatial expression patterns of annexins I-VI were evaluated in the rat dorsal root ganglia (DRG) and spinal cord (SC) by using indirect immunofluorescence. Annexin I is expressed in small sensory neurons of the DRG, by most neurons of the SC, and by ependymal cells lining the central canal. Annexin II is expressed by most sensory neurons of the DRG but is primarily expressed in the SC by glial cells. Annexin III is expressed by most sensory neurons, regardless of size, by endothelial cells lining the blood vessels, and by the perineurium. In the SC, annexin III is primarily expressed by astrocytes. In the DRG and the SC, annexin IV is primarily expressed by glial cells and at lower levels by neurons. In the DRG, annexin V is expressed in relatively high concentrations in small sensory neurons in contrast to the SC, where it is expressed mainly by ependymal cells and by small-diameter axons located in the superficial laminae of the dorsal horn areas. Annexin VI is differentially expressed by sensory neurons of the DRG, being more concentrated in small neurons. In the SC, annexin VI has the most striking distribution. It is concentrated subjacent to the plasma membrane of motor neurons and their processes. The differential localization pattern of annexins in cells of the SC and DRG could reflect their individual biological roles in Ca(2+)-signal transduction within the central nervous system.

Annexins are a large group of calcium-dependent cytoskeletal- and membrane-associated proteins whose properties include cytoskeleton and phospholipid binding and mitotic signal transduction. Although annexin-like molecules have been reported on the external plasma membranes of certain cells, in general they are considered to be cytoplasmic proteins. We report here the heterogenous expression of certain annexins (I-VI) on the external cell surfaces of non-metastatic and metastatic murine (RAW117 large-cell lymphoma), rat (13762NF mammary adenocarcinoma) and some human (KM12 and HT29 colorectal carcinoma) cell lines but not on some other cell lines such as human (A375 and MeWo) and mouse (B16) melanoma. The implication of annexin cell surface expression in the metastatic process is discussed with respect to tumor cell adhesion.

Calcium-dependent regulation of cellular processes is mediated by specific intracellular proteins. A newly described set of proteins isolated from chicken gizzard with Mr of 67 X 10(3), 35 X 10(3), 33 X 10(3) and 30 X 10(3) also express a hydrophobic site in the presence of calcium. These proteins are isolated from several other cellular tissues and are termed calcimedins. These proteins differ from calmodulin in isoelectric point, DEAE-cellulose binding characteristics and heat stability. The calcimedins do not activate calmodulin-dependent cyclic nucleotide phosphodiesterase but do activate a hepatic microsomal Ca2+ -ATPase system. Hence, the possibility is opened that calcium regulation of cellular processes is mediated by calcium-binding proteins in addition to calmodulin.

Reports that phosphorylation mutants elucidate the mechanism of annexin IV-mediated membrane aggregation. Liposome binding and aggregation; 2D electron crystallography and cryo-electron microscopy; Three-dimensional crystallographic analysis of T6D annexin IV.