Cell Biology of Annexins: Ubiquitous Players in Membrane Structure, Signaling, Repair and Exosome Biology

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About this Research Topic

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Background

The protein family of annexins was discovered more than 4 decades ago and the characterization of their unique properties, binding phospholipid-containing cellular membranes in a Ca2+-dependent manner, made them ideal candidates to integrate Ca2+ signaling and membrane dynamics. Accordingly, annexins have been associated with a wide variety of molecular events in cell biology. In recent years, novel roles for annexins and their molecular details in membrane organization, often related to stress conditions, have been emerging, often relevant in pathological settings and providing novel therapeutic opportunities.

Annexins represent 12 structurally related Ca2+- and phospholipid-binding proteins in humans and vertebrates. Based on their membrane binding features, their role in membrane organization has been proposed, but evidence for annexins modulating either the lipid composition of membrane domains, and/or altering membrane domain function, has been limited. In recent years, the ability of annexins to rapidly respond to localized changes of Ca2+ levels, but also alterations in phospholipid and cholesterol distribution, has been linked to stress-associated molecular consequences relevant for membrane repair, membrane trafficking and signaling, but also exosome formation.

To reflect these current developments, this special issue aims to provide some recent advances in the field, with a special emphasis on how annexin regulation/adaptation of membrane trafficking can be affected in the context of different diseases. This includes novel insights based on the analysis of interactomes of individual annexins, as well as the role of annexins in facilitating cell-cell communication via exosomes. This topic also aims to identify and addresses the major gaps and lack of molecular insights that have yet to be clarified to decipher the molecular functions of this exciting protein family, with the ultimate goal to spark efforts to bridge the gap between mechanistic understanding and translational use for novel annexin-based diagnostic tools and therapeutic approaches.

Areas to be covered in this Research Topic may include, but are not limited to the following. These may be considered in the context of health and disease:

• The interplay of annexins and membrane trafficking (e.g. exosome formation, modulation of membrane composition, altering membrane domain function, etc.)
• Annexin interactomes and their topology in exosomes
• Annexins in the context of signaling
• Molecular insights of annexins (e.g. protein-protein/protein-lipid interaction)
• Discussions around major gaps and lack of molecular insights that have yet to be clarified

Keywords: annexins, membrane organisation, calcium signalling, cellular stress, membrane repair, exosomes

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