The p11/S100A10 light chain of annexin A2 is dispensable for annexin A2 association to endosomes and functions in endosomal transport.
BACKGROUND
Annexin A2 is a peripheral membrane protein that belongs to the annexin family of Ca(2+) and phospholipid-binding proteins. This protein, which plays a role in membrane organization and dynamics in particular along the endocytic pathway, exists as a heterotetrameric complex, consisting of two annexin A2 molecules bound via their N-termini to a dimer of p11/S100A10 light chains. The light chain, and thus presumably formation of the heterotetramer, was reported to control annexin A2 association to the plasma membrane and to cortical actin, as well as the distribution of recycling endosomes. However, the specific role of the light chain and the functions of monomeric versus heterotetrameric annexin A2 have remained elusive in the endocytic pathway.


RESULTS
Here, we have investigated whether p11 plays a role in the endosomal functions of annexin A2. Using morphological and biochemical approaches, we found that p11, unlike annexin A2, was not present on early endosomes. Neither was the heterotetramer detected on purified early endosomes, while it was clearly present in total cell lysates. Moreover, knockdown of p11 with siRNAs did not affect annexin A2 targeting to early endosomes, and, conversely, binding of annexin A2 to purified endosomes or liposomes occurred without p11 in vitro. Finally, while we could confirm that annexin A2 knockdown inhibits transport beyond early endosomes, p11 knockdown had no such effects on early-to-late endosome transport.


CONCLUSIONS
Our data show that the binding of annexin A2 to endosomal membranes and its role in endosomal trafficking are independent of the p11/S100A10 light chain. We thus conclude that annexin A2 functions are fully supported by the monomeric form of the protein, at least the endocytic pathway leading to lysosomes.
Morel
Etienne
E
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
Gruenberg
Jean
J
D000818:Animals; D017306:Annexin A2 / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism; D013347:Subcellular Fractions; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D002118:Calcium; D006023:Glycoproteins; D008081:Liposomes; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C472822:ANXA2 protein, human