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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 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.

Titel: A New Mint1 Isoform, but Not the Conventional Mint1, Interacts with the Small GTPase Rab6
Verfasser: Thyrock, Anika GND
Ossendorf, Edith
Stehling, Martin GND
Kail, Mark
Kurtz, Tanja GND
Pohlentz, Gottfried GND
Waschbüsch, Dieter GND
Eggert, Simone GND
Formstecher, Etienne
Müthing, Johannes GND
Dreisewerd, Klaus GND
Kins, Stefan GND
Goud, Bruno
Barnekow, Angelika GND
Organisation: FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 30.05.2013
Publikation in MIAMI: 10.02.2014
Datum der letzten Änderung: 16.04.2019
Quelle: PLoS ONE 8 (2013) 5, e64149
Fachgebiete: Biowissenschaften; Biologie
Lizenz: CC BY 3.0
Sprache: Deutsch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2013/2014 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-34329408912
Permalink: https://nbn-resolving.org/urn:nbn:de:hbz:6-34329408912
DOI: 10.1371/journal.pone.0064149
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