Annexins—a family of proteins with distinctive tastes for cell signaling and membrane dynamics

Abstract

Annexins are cytosolic proteins with conserved three-dimensional structures that bind acidic phospholipids in cellular membranes at elevated Ca2+ levels. Through this they act as Ca2+-regulated membrane binding modules that organize membrane lipids, facilitating cellular membrane transport but also displaying extracellular activities. Recent discoveries highlight annexins as sensors and regulators of cellular and organismal stress, controlling inflammatory reactions in mammals, environmental stress in plants, and cellular responses to plasma membrane rupture. Here, we describe the role of annexins as Ca2+-regulated membrane binding modules that sense and respond to cellular stress and share our view on future research directions in the field.

Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

“…The large family of annexin proteins show a very heterogeneous cell- and tissue-specific expression pattern. 17 Here, we identified annexin A4 as specifically enriched in tumor cells of clear cell renal cell carcinoma (ccRCC), in line with previous studies reporting increased protein levels of ANXA4. 23,39 Given the context- and cell-type dependent role of individual annexins, a comprehensive functional characterization of ANXA4 in ccRCC was to date missing.…”

“…23,39 Given the context- and cell-type dependent role of individual annexins, a comprehensive functional characterization of ANXA4 in ccRCC was to date missing. 17 In this study, we demonstrated that ANXA4 exhibits distinct subcellular localization patterns related to separate biological function such as membrane repair as well as modulation of transcriptional signatures employing in vitro, in silico and in situ approaches.…”

“…16 ANXA proteins show a tissue- and cell-type specific expression profile, where the majority of respective proteins is detectable in epithelial cells. 17 Given their wide propensity to interact with phospholipids of cellular membranes (e.g. plasma membrane), ANXA proteins have been implicated in a wide variety of pathologies ranging from inflammation, vascular homeostasis, neurological diseases as well as cancer.…”

Annexin- and calcium-regulated priming of legume root cells for endosymbiotic infection

“…MtAnn1 is a cytosolic phospholipid-and Ca 2+ -interacting protein of the annexin family 13 , viewed as dynamic regulators that associate with membranes when intracellular Ca 2+ levels change 15,16 . Annexin family members are involved in the regulation of ion transport, modulation of cytoplasmic Ca 2+ signals and ROS signalling in diverse abiotic or biotic responses [71][72][73][74][75] .…”

“…The rhizobia-and AM-induced MtAnn1 13 and MtAnn2 14 genes, which encode cytosolic Ca 2+ binding annexins that can bind to membranes to modulate a variety of Ca 2+ -regulated processes (e.g. ion conductance, exocytosis/endocytosis) 15,16 , are potential players in this process.…”