Moreover, in addition to its functions in the degradation pathway leading to late endosomes and lysosomes, AnxA2 also plays a role in the recycling pathway, perhaps as a heterotetramer. In addition, it has also been suggested that annexin A1, which is closely related to AnxA2, is targeted to early endosomes with its light chain p10/S100C/S100A11, most probably as a tetrameric complex. Here, we demonstrate that AnxA2 functions in endosomal membrane transport do not depend on the light chain p11. Temozolomide supply Previous studies from others and us have shown that AnxA2 association to early endosomes does not depend on calcium ions but on membrane cholesterol, and requires the small N-terminal domain of the protein, which contains the p11 binding site and the phosphorylation sites. This is further illustrated by the fact that the core domain alone does not bind bilayers in the absence of calcium. One might thus envision that the N-terminal region of AnxA2 cannot accommodate p11 spatially while fulfilling the endosomal functions of the protein. The short AnxA2 N-terminus may form an amphipathic helix, and structural studies revealed that p11 binds an Nterminal AnxA2 peptide through hydrophobic interactions. It is thus conceivable that, in the absence of p11, the N-terminal amphipathic helix dips into the bilayer and interacts with lipid tails and perhaps cholesterol itself. Future work will clearly be necessary to determine why the p11 light chain seems dispensable for AnxA2 functions in the degradation pathway, while the 2- 2 heterotetramer plays a role in the subcellular distribution of early and recycling endosomes. One might, however, speculate that calcium-dependent membrane association, e.g. at the plasma membrane or along the protein recycling pathway, are regulated by p11 binding and heterotetramer formation. Indeed, the p11 light chain appears to be necessary for AnxA2 binding to the plasma membrane and to the cortical actin network, both mechanisms being also regulated by the presence of Ca2+. In addition, 2- 2 association to the plasma membrane seems to be regulated by direct binding of the heterotetramer to phosphatidylinositol bisphosphate and p11 itself seems to play a role in the trafficking of some ion Niraparib channels and receptors �� reviewed in. Rescher and Gerke thus recently proposed that p11 tethers some transmembrane proteins to AnxA2, and thereby anchors them at specific membrane sites or helps their transport to the plasma membrane. It is conceivable that specific functions of AnxA2 are differentially regulated at different sites and along different trafficking routes by separate mechanisms. The human immunodeficiency virus type 1 envelope glycoprotein is the lone viral gene product exposed on surface of the virus and therefore is the major target of HIV-1-specific neutralizing antibodies.