SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and clathrin assembly protein and functions on the AP-1-positive early endosome/trans-Golgi network.
We recently reported that SMAP1, a GTPase-activating protein (GAP) for Arf6, directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane. Here, we identified a SMAP1 homologue that we named SMAP2. Like SMAP1, SMAP2 exhibits GAP activity and interacts with clathrin heavy chain (CHC). Furthermore, we show that SMAP2 interacts with the clathrin assembly protein CALM. Unlike SMAP1, however, SMAP2 appears to be a regulator of Arf1 in vivo, because cells transfected with a GAP-negative SMAP2 mutant were resistant to brefeldin A. SMAP2 colocalized with the adaptor proteins for clathrin AP-1 and EpsinR on the early endosomes/trans-Golgi-network (TGN). Moreover, overexpression of SMAP2 delayed the accumulation of TGN38/46 molecule on the TGN. This suggests that SMAP2 functions in the retrograde, early endosome-to-TGN pathway in a clathrin- and AP-1-dependent manner. Thus, the SMAP gene family constitutes an important ArfGAP subfamily, with each SMAP member exerting both common and distinct functions in vesicle trafficking.
Department of Molecular Immunology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan.
Waka
W
Natsume
Kenji
K
Tanabe
Shunsuke
S
Kon
Naomi
N
Yoshida
Toshio
T
Watanabe
Tetsuo
T
Torii
Masanobu
M
Satake
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism*; D011992:Endosomes / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D021601:trans-Golgi Network / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D002966:Clathrin; C476827:SMOC2 protein, human; D018808:Transcription Factor AP-1