SARA, a FYVE domain protein, affects Rab5-mediated endocytosis.
Rab5, a member of the small GTPase family of proteins, is primarily localized on early endosomes and has been proposed to participate in the regulation of early endosome trafficking. It has been reported that phosphatidylinositol 3-kinases and FYVE domain proteins, such as EEA1, can be recruited onto early endosomes and act as Rab5 effectors. SARA (Smad anchor for receptor activation), also a FYVE domain protein, was initially isolated as a participant in signal transduction from the transforming growth factor beta receptor. Overexpressed SARA has been found on EEA1-positive early endosomes. In this report, we show that endogenous SARA is present on early endosomes and overexpression of SARA causes endosomal enlargement. Functionally, SARA overexpression significantly delays the recycling of transferrin. The transferrin receptor distributed on the cell surfaces was also greatly reduced in cells overexpressing SARA. However, the internalization rate of transferrin is not affected by SARA overexpression. The morphological and functional alterations caused by SARA overexpression resemble those caused by overexpression of Rab5:GTP mutant Rab5Q79L. Finally, all SARA-mediated phenotypic changes can be counteracted by overexpression Rab5:GDP mutant Rab5S34N. These results collectively suggested that SARA plays an important functional role downstream of Rab5-regulated endosomal trafficking.
Hu
Yang
Y
Graduate Program of Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Chuang
Jen-Zen
JZ
Xu
Kai
K
McGraw
Timothy G
TG
Sung
Ching-Hwa
CH
D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D021381:Protein Transport; D012697:Serine Endopeptidases; D015398:Signal Transduction; D014168:Transferrin / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014168:Transferrin; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases; D020696:rab5 GTP-Binding Proteins