MARCH-II is a syntaxin-6-binding protein involved in endosomal trafficking.
Membrane-associated RING-CH (MARCH) is a recently identified member of the mammalian E3 ubiquitin ligase family, some members of which down-regulate the expression of immune recognition molecules. Here, we have identified MARCH-II, which is ubiquitously expressed and localized to endosomal vesicles and the plasma membrane. Immunoprecipitation and in vitro binding studies established that MARCH-II directly associates with syntaxin 6. Overexpression of MARCH-II resulted in redistribution of syntaxin 6 as well as some syntaxin-6-interacting soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) into the MARCH-II-positive vesicles. In addition, the retrograde transport of TGN38 and a chimeric version of furin to trans-Golgi network (TGN) was perturbed--without affecting the endocytic degradative and biosynthetic secretory pathways--similar to effects caused by a syntaxin 6 mutant lacking the transmembrane domain. MARCH-II overexpression markedly reduced the cell surface expression of transferrin (Tf) receptor and Tf uptake and interfered with delivery of internalized Tf to perinuclear recycling endosomes. Depletion of MARCH-II by small interfering RNA perturbed the TGN localization of syntaxin 6 and TGN38/46. MARCH-II is thus likely a regulator of trafficking between the TGN and endosomes, which is a novel function for the MARCH family.
Nakamura
Nobuhiro
N
Department of Biological Sciences, Tokyo Institute of Technology, Yokohama, Japan.
Fukuda
Hidekazu
H
Kato
Akira
A
Hirose
Shigehisa
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006224:Cricetinae; D015536:Down-Regulation; D011992:Endosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D050765:Qa-SNARE Proteins; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D050600:SNARE Proteins; D044767:Ubiquitin-Protein Ligases; D033921:Vesicular Transport Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D011990:Receptors, Transferrin; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D004815:Epidermal Growth Factor; C502926:MARCHF2 protein, human; C502927:Marchf2 protein, rat; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors