Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.
Bottom Line: Compared with wild-type mouse perivascular cells, AnxA5- cells exhibit a severe membrane repair defect.In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair.We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.
Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.Show MeSH
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Mentions: Annexins form a family of soluble proteins that bind to membranes exposing negatively charged phospholipids, particularly phosphatidylserine (PS), in a Ca2+-dependent manner17. Annexins are formed by a four- (exceptionally eight-) fold repeat of 70 amino-acid domains that are highly conserved and by a variable amino (N)-terminal domain, which is assumed to be responsible for their functional specificities18. Following the determination of AnxA5 structure by Huber et al.19, atomic models have been obtained for several other annexins20. These structures show that annexins consist of a common membrane-binding core, which has the shape of a slightly curved rhomboid19 with a convex membrane-binding face that presents Ca2+-binding loops and a concave face from which protrudes the N-terminal domain. The membrane-binding core is made of the cyclic arrangement of four α-helical domains, which correspond to the conserved sequence domains (Fig. 1a). Despite a wealth of studies describing the membrane-related properties of annexins, their biological functions remain largely unknown. Several reports have proposed intracellular functions for annexins, mainly AnxA2 in vesicle trafficking and membrane organization17. Paradoxically, although they lack a secretory signal peptide, annexins are found both intracellularly and extracellularly. Actually, the best-defined functions of the annexins concern extracellular AnxA1, AnxA2 and AnxA5, which possess anti-inflammatory21, pro-fibrinolytic22 and anti-thrombotic23 activities, respectively. A distinctive property of AnxA5 and several other annexins is to self-assemble into two-dimensional (2D) ordered arrays on membrane binding17242526272829303132. In the presence of mM Ca2+ concentration, AnxA5 molecules bind to PS-containing membranes and self-assemble rapidly into trimers333435 and 2D ordered arrays of trimers2427293235 (Fig. 1b). Annexin arrays have been proposed to participate in the regulation of membrane organization and dynamics1735 and, in the case of AnxA5, to form an anticoagulant shield covering the surface of placental syncytiotrophoblasts23.
Affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN CNRS-University Bordeaux1-ENITAB, Talence F-33402, France.