Plasma membrane-bound sialidase Neu3 impairs clathrin-mediated endocytosis

RODRIGUEZ WALKER M.; VILCAES A.; DANIOTTI J.L.

Buenos Aires

Simposio; First Argentinian Symposium of Glycobiology GlycoAR 2014; 2014

Local Organizing committee

Gangliosides (GS) are sialic acid-containing glycolipids expressed on plasma membrane (PM). They participate in a variety of cellular events, such as cell adhesion and endocytosis. Neu3, a key sialidase for GS hydrolysis, has been implicated in similar biological processes as GS. However, the precise role of Neu3 and GS on endocytic processes has not been well established. We found an increase in the internalization of transferrin (Tf) via clathrin (CL)-mediated endocytosis in cells expressing GS with higher levels of sialylation. The expression of Neu3 led to a drastic reduction in Tf endocytosis and sorting, suggesting a participation of GS in this process. However, the expression of Neu3 maintained its effect on Tf endocytosis in cells with reduced levels of GS expression. CL-mediated endocytosis of LDL was also decreased after Neu3 expression, while the internalization of Cholera toxin, via a CL-independent pathway, was not modified. In addition, Neu3 caused a reduction of Tf content in early endosomes while Tf binding was slightly affected at the PM level. Interestingly, we found that the effect produced by Neu3 on CL-mediated endocytosis involved an abnormal distribution of CL adaptor AP2, whereas the intracellular distribution of CL and caveolin remained without changes. Overall, the results suggest a specific and novel role of Neu3 on CL-mediated endocytosis.