Intracellular Ca2q signalling and Ca2q homeostasis are among the central problems in cell biology that have received major attention for a number of decades. Fascinating and intricate signalling pathways and modes of regulation have emerged from research in this area, boosting among other things our understanding of the regulation of intracellular Ca2q levels through specific channels and pumps located in the plasma membrane and in the membranes of intracellular organelles. Conceptually, proteins involved directly in Ca2q signalling and Ca2q homeostasis should be able to bind the divalent cation and considerable effort has been put into the identification of such Ca2q effector proteins. In fact, a vast number of intracellular Ca2q binding proteins are known to date, only a few of them, however, having a clear function assigned to them. Among the Ca2q binding proteins whose function still is enigmatic are the annexins, a discrete multigene family of Ca2q binding proteins characterized by their ability to interact Ca2q dependently with membrane phospholipids. Properties and potential functions of annexins will be discussed in this review which will put a particular emphasis on recent developments and the putative roles of annexins in cellular physiology and membrane biology.

A typical annexin protein is characterized by two distinct features: it exhibits Ca2q-dependent binding to phospholipids, preferentially acidic phospholipids containing one to several negative charges, and it contains as a conserved sequence element the annexin repeat, a segment of some 70 amino acids which is repeated four or eight times in a given member of the family. Thus, biochemical and gene cloning approaches have led to the formulation of the annexin characteristics and to the classification of a given protein or gene as an annexin. Moreover, such approaches have proven very helpful to identify annexins, which were initially described in higher vertebrates, in a larger number of other organisms ranging from lower vertebrates to insects, nematodes and plants. While very distinct structural and biochemical criteria define an annexin, proteins of this multigene family have been implicated in a wide range of biological processes often but not always related to membranes. These include the regulation of mem-