HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yokozeki, T. Articles by Sehara-Fujisawa, A. Search for Related Content PubMed Articles by Yokozeki, T. Articles by Sehara-Fujisawa, A.

¹ Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
² Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
³ Amgen, 1201 Amgen Court West, Seattle, WA 98119-3105, USA

Membrane-anchored Neuregulin ß1 sheds its ectodomain as soluble factors. Two proteases that belong to a disintegrin and metalloprotease (ADAM) family are known to cleave Neuregulin ß1. One is tumor necrosis factor- converting enzyme (TACE/ADAM17). The other is Meltrin ß (ADAM19). Against our expectation that shedding by ADAM proteases occurs at the cell surface, here we found that Meltrin ß mediates the ectodomain shedding of Neuregulin ß1 in the Golgi apparatus. Meltrin ß was localized in and around the Golgi apparatus in developing sensory neurons. Subcellular fractionation revealed that Meltrin ß generated soluble Neuregulin ß1 in Golgi-enriched fractions while TACE-cleaved Neuregulin ß1 was recovered in lighter fractions. To examine whether Meltrin ß-mediated ectodomain shedding occurs in the Golgi apparatus in living cells, we took advantage of different diffusion properties of cleavage products from those of membrane-anchored precursor proteins. Fluorescence correlation spectroscopy (FCS) is the most sensitive method to determine millisubmillisecond diffusion in vivo. Protease-active Meltrin ß caused a shift in autocorrelation function in FCS of green fluorescent protein (GFP)-tagged Neuregulin ß1 in the Golgi apparatus, suggesting a conversion of Neuregulin ß1 molecules from membrane-anchored to soluble forms in that organelle. The Golgi apparatus is a site of processing Neuregulin ß1 by Meltrin ß.

^* Correspondence: E-mail: iwada{at}fmu.ac.jp; asehara{at}frontier.kyoto-u.ac.jp