Ferlins Show Tissue-Specific Expression and Segregate as Plasma Membrane/Late Endosomal or Trans-Golgi/Recycling Ferlins
| Autor: | Reece A. Sophocleous, Sandra T. Cooper, Cynthia B. Whitchurch, Gregory M. I. Redpath, Lynne Turnbull |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vesicle fusion biology Endosome Endocytic cycle Cell Biology Subcellular localization Biochemistry Synaptotagmin 1 Cell biology Dysferlin 03 medical and health sciences 030104 developmental biology Structural Biology Cytoplasm Genetics biology.protein Molecular Biology Late endosome |
| Zdroj: | Traffic. 17:245-266 |
| ISSN: | 1398-9219 |
| DOI: | 10.1111/tra.12370 |
| Popis: | Ferlins are a family of transmembrane-anchored vesicle fusion proteins uniquely characterized by 5-7 tandem cytoplasmic C2 domains, Ca(2+)-regulated phospholipid-binding domains that regulate vesicle fusion in the synaptotagmin family. In humans, dysferlin mutations cause limb-girdle muscular dystrophy type 2B (LGMD2B) due to defective Ca(2+)-dependent, vesicle-mediated membrane repair and otoferlin mutations cause non-syndromic deafness due to defective Ca(2+)-triggered auditory neurotransmission. In this study, we describe the tissue-specific expression, subcellular localization and endocytic trafficking of the ferlin family. Studies of endosomal transit together with 3D-structured illumination microscopy reveals dysferlin and myoferlin are abundantly expressed at the PM and cycle to Rab7-positive late endosomes, supporting potential roles in the late-endosomal pathway. In contrast, Fer1L6 shows concentrated localization to a specific compartment of the trans-Golgi/recycling endosome, cycling rapidly between this compartment and the PM via Rab11 recycling endosomes. Otoferlin also shows trans-Golgi to PM cycling, with very low levels of PM otoferlin suggesting either brief PM residence, or rare incorporation of otoferlin molecules into the PM. Thus, type-I and type-II ferlins segregate as PM/late-endosomal or trans-Golgi/recycling ferlins, consistent with different ferlins mediating vesicle fusion events in specific subcellular locations. |
| Databáze: | OpenAIRE |
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