Figure 8.

Model illustrating the regulation of ADAM9 by intracellular trafficking. Newly synthesized pro-ADAM9 is matured during secretion to the cell surface by prodomain cleavage in the Golgi compartment. Mature cell-surface localized ADAM9 is then constitutively internalized via a clathrin-dependent mechanism, followed by either recycling or intracellular degradation. Our findings indicate that an interaction between ADAM9 and the intracellular sorting proteins SNX9 or SNX18 is required for optimal internalization. Moreover, SNX9 may have an additional effect, binding pro-ADAM9 in an intracellular compartment (possibly Golgi) to regulate its processing. Combined, SNX9 serves to restrict the amount of ADAM9 and hence ADAM9-mediated shedding activities at the cell surface.