A New Mint1 Isoform, but Not the Conventional Mint1, Interacts with the Small GTPase Rab6

Small GTPases of the Rab family are important regulators of a large variety of different cellular functions such as membrane organization and vesicle trafficking. They have been shown to play a role in several human diseases. One prominent member, Rab6, is thought to be involved in the development o...

Authors: Thyrock, Anika
Ossendorf, Edith
Stehling, Martin
Kail, Mark
Kurtz, Tanja
Pohlentz, Gottfried
Waschbüsch, Dieter
Eggert, Simone
Formstecher, Etienne
Müthing, Johannes
Dreisewerd, Klaus
Kins, Stefan
Goud, Bruno
Barnekow, Angelika
Division/Institute:FB 13: Biologie
Document types:Article
Media types:Text
Publication date:2013
Date of publication on miami:10.02.2014
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:PLoS ONE 8 (2013) 5, e64149
DDC Subject:570: Biowissenschaften; Biologie
License:CC BY 3.0
Language:German
Notes:Finanziert durch den Open-Access-Publikationsfonds 2013/2014 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-34329408912
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-34329408912
Other Identifiers:DOI: 10.1371/journal.pone.0064149
Digital documents:journal.pone.0064149.pdf

Small GTPases of the Rab family are important regulators of a large variety of different cellular functions such as membrane organization and vesicle trafficking. They have been shown to play a role in several human diseases. One prominent member, Rab6, is thought to be involved in the development of Alzheimer’s Disease, the most prevalent mental disorder worldwide. Previous studies have shown that Rab6 impairs the processing of the amyloid precursor protein (APP), which is cleaved to β-amyloid in brains of patients suffering from Alzheimer’s Disease. Additionally, all three members of the Mint adaptor family are implied to participate in the amyloidogenic pathway. Here, we report the identification of a new Mint1 isoform in a yeast two-hybrid screening, Mint1 826, which lacks an eleven amino acid (aa) sequence in the conserved C-terminal region. Mint1 826, but not the conventional Mint1, interacts with Rab6 via the PTB domain. This interaction is nucleotide-dependent, Rab6-specific and influences the subcellular localization of Mint1 826. We were able to detect and sequence a corresponding proteolytic peptide derived from cellular Mint1 826 by mass spectrometry proving the absence of aa 495–505 and could show that the deletion does not influence the ability of this adaptor protein to interact with APP. Taking into account that APP interacts and co-localizes with Mint1 826 and is transported in Rab6 positive vesicles, our data suggest that Mint1 826 bridges APP to the small GTPase at distinct cellular sorting points, establishing Mint1 826 as an important player in regulation of APP trafficking and processing.