Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking
Autor: | Nicole Hübel, Angelika Barnekow, Veerle Baekelandt, Evy Lobbestael, Mary W. McCaffrey, Amir R. Khan, Edith Ossendorf, Andrew J. Lindsay, Dieter Waschbüsch |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Retromer Hydrolases Immunofluorescence Fluorescent Antibody Technique Golgi Apparatus PROTEIN Membrane trafficking GTPase Biochemistry VPS35 0302 clinical medicine Medicine and Health Sciences Post-Translational Modification Phosphorylation Sorting Nexins Materials Staining Movement Disorders Secretory Pathway Multidisciplinary Chemistry Cell Staining Neurodegenerative Diseases Parkinson Disease LRRK2 Enzymes Cell biology Multidisciplinary Sciences Protein Transport Neurology Cell Processes Physical Sciences symbols Medicine Science & Technology - Other Topics Cellular Structures and Organelles Protein Binding trans-Golgi Network Research Article Endosome Science Amorphous Solids Blotting Western Materials Science EARLY/RECYCLING ENDOSOMES Research and Analysis Methods Cell Line 03 medical and health sciences symbols.namesake Two-Hybrid System Techniques Cellular dynamics Humans Immunoprecipitation Immunoassays Science & Technology COMPLEX IDENTIFICATION RECOGNITION Biology and Life Sciences Proteins Cell Biology Golgi apparatus EMERGING ROLE Rab TRANSPORT nervous system diseases Guanosine Triphosphatase 030104 developmental biology GTPASES rab GTP-Binding Proteins Specimen Preparation and Treatment SUBUNIT Enzymology Immunologic Techniques Sorting nexin 6 Glass 030217 neurology & neurosurgery |
Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 1, p e0208889 (2019) |
Popis: | The Rab family of small GTPases regulate various aspects of cellular dynamics in eukaryotic cells. Membrane trafficking has emerged as central to the functions of leucine-rich repeat kinase 2 (LRRK2), which is associated with inherited and sporadic forms of Parkinson's disease (PD). Rabs act as both regulators of the catalytic activity and targets for serine/threonine phosphorylation by LRRK2. Rab32, Rab38 and Rab29 have been shown to regulate LRRK2 sub-cellular localization through direct interactions. Recently, Rab29 was shown to escort LRRK2 to the Golgi apparatus and activate the phosphorylation of Rab8 and Rab10. Rab32 is linked to multiple cellular functions including endosomal trafficking, mitochondrial dynamics, and melanosome biogenesis. A missense mutation in Rab32 has also recently been linked to PD. Here, we demonstrate that Rab32 directly interacts with sorting nexin 6 (SNX6). SNX6 is a transient subunit of the retromer, an endosome-Golgi retrieval complex whose Vps35 subunit is strongly associated with PD. We could further show that localization of cation-independent mannose-6-phosphate receptors, which are recycled to the trans-Golgi network (TGN) by the retromer, was affected by both Rab32 and SNX6. These data imply that Rab32 is linked to SNX6/retromer trafficking at the Golgi, and also suggests a possible connection between the retromer and Rab32 in the trafficking and biological functions of LRRK2. ispartof: PLoS One vol:14 issue:1 ispartof: location:United States status: published |
Databáze: | OpenAIRE |
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