The Arf GTPase-activating protein SMAP1 promotes transferrin receptor endocytosis and interacts with SMAP2

• The SMAP subfamily of Arf GAPs has two members, SMAP1 and SMAP2.
• Both SMAP1 and SMAP2 play positive roles in endocytosis of transferrin receptor.
• SMAP1 and SMAP2 physically interact with each other through their C-terminal domains.
• SMAP1 and SMAP2 are colocalized on endosomal structures.
• The two proteins have an overlapping function in addition to distinct functions.

Arf GTPase-activating proteins (Arf GAP) play important roles in the formation of the membrane vesicles that traffic between subcellular membranous organelles. The small Arf GTPase-activating protein (SMAP) subfamily of Arf GAPs has two members, SMAP1 and SMAP2, in mammals. The present study investigated whether these two proteins may have an overlapping function in addition to their previously reported distinct functions. Results showed that the presence of either SMAP1 or SMAP2 was sufficient for endocytosis of the transferrin receptor, and that transferrin incorporation was impaired only by the absence of both SMAP1 and SMAP2. This suggests the involvement of both SMAP1 and SMAP2 in transferrin endocytosis. Results also demonstrated a physical association between SMAP1 and SMAP2, which might serve as a basis for a functional interaction, and identified the intramolecular domains responsible for this association.