Annexins in cell membrane dynamics: Ca2+-regulated association of lipid microdomains

The sarcolemma of smooth muscle cells is composed of alternating stiff acti n-binding, and flexible caveolar domains. In addition to these stable macro -domains, the plasma membrane contains dynamic glycosphingolipid- and chole sterol-enriched microdomains, which act as sorting posts for specific prote ins and art: involved in membrane trafficking and signal transduction. We d emonstrate that these lipid rafts are neither periodically organized nor ex clusively confined to the actin attachment sites or caveolar regions. Chang es in the Ca2+ concentration that are affected during smooth muscle contrac tion lead to important structural rearrangements within the sarcolemma, whi ch can be attributed to members of the annexin protein family. We show that the associations of annexins II,V, and VI with smooth muscle microsomal me mbranes exhibit a high degree of Ca2+ sensitivity, and that the extraction of annexins II and VI by detergent is prevented by elevated Ca2+ concentrat ions. Annexin VI participates in the formation of a reversible, membrane-cy toskeleton complex (Babiychuk, E.B., R.J. Palstra, J. Schaller, U. Kampfer, and A. Draeger. 1999. J. Biol. Chem. 274:35191-35195). Annexin II promotes the Ca2+-dependent association of lipid raft microdomains, whereas annexin V interacts with glycerophospholipid microcompartments. These interactions bring about a new configuration of membrane-bound constituents, with poten tially important consequences for signaling events and Ca2+ flux.