VIP36 protein is a target of ectodomain shedding and regulates phagocytosis in macrophage Raw 264.7 cells.
Ectodomain shedding is a posttranslational modification mechanism, which liberates extracellular domains of membrane proteins through juxtamembrane processing executed mainly by the ADAM (a disintegrin and metalloprotease) family of metalloproteases. Shedding is a unique and effective mechanism for inducing multifaceted effects through the soluble extracellular domains released and/or the remaining membrane-bound portions; however, the physiological functions of shedding are not yet fully understood. In this study, we performed unbiased proteomic screening for shedding targets in a lipopolysaccharide (LPS)-stimulated macrophage cell line to elucidate a new immunological function of shedding. We identified VIP36 (36-kDa vesicular integral membrane protein), a lectin domain-containing transmembrane protein postulated as a cargo receptor for Golgi-to-endoplasmic reticulum transport, as a new target for shedding and found that the shedding of VIP36 occurs mainly on the cell surface. In addition, we demonstrate that the amount of VIP36 precisely regulates phagocytosis in macrophages and that the shedding of VIP36 is required for this regulation. These results substantially expand our knowledge of the immunological and cell biological functions of both the shedding process and VIP36 itself.
Center for Integrated Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. kshira@z8.keio.jp
Kyoko
K
Shirakabe
Seisuke
S
Hattori
Motoharu
M
Seiki
Shigeo
S
Koyasu
Yasunori
Y
Okada
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods
C086797:LMAN2 protein, human; D037241:Mannose-Binding Lectins; D026901:Membrane Transport Proteins