Trafficking of Human ADAM 12-L: Retention in the trans-Golgi Network

• Published in: Biochemical and biophysical research communications Vol. 275; no. 2; pp. 261 - 267
• Main Authors: Hougaard, Susanne, Loechel, Frosty, Xu, Xiufeng, Tajima, Rie, Albrechtsen, Reidar, Wewer, Ulla M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.08.2000
• Subjects: ADAM 12; ADAM Proteins; ADAM12 Protein; Animals; Biological Transport; Cell Compartmentation; Cell Membrane - metabolism; CHO Cells; COS Cells; Cricetinae; Cytoplasm - metabolism; disintegrin; Golgi Apparatus - metabolism; HeLa Cells; Humans; Immunohistochemistry; Membrane Proteins - biosynthesis; Membrane Proteins - metabolism; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - metabolism; metalloprotease; Microscopy, Fluorescence; Octoxynol; trafficking; trans-Golgi network; disintegrin; metalloprotease; ADAM 12; trafficking; trans-Golgi network
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3295

We have investigated the trafficking of the membrane-anchored form of human ADAM 12 (ADAM 12-L) fused to a green fluorescence protein tag. Subcellular localization of the protein in transiently transfected cells was determined by fluorescence microscopy and trypsin sensitivity. Full-length ADAM 12-L was retained in a perinuclear compartment, which was shown to be the trans-Golgi network. In contrast, ADAM 12-L lacking the cytoplasmic domain reached the cell surface. Based on analysis of deletions and mutations of the cytoplasmic tail of ADAM 12-L, the retention signal is comprised of both the cytoplasmic and transmembrane domains, but not the Src homology 3 domain (SH3) binding sites. These results raise the possibility that a trafficking checkpoint in the trans-Golgi network is one of the cellular mechanisms for regulation of ADAM 12-L function, by allowing a rapid release of ADAM 12-L to the cell surface under specific stimuli.