| Title: |
Ferlins Show Tissue‐Specific Expression and Segregate as Plasma Membrane/Late Endosomal or Trans‐Golgi/Recycling Ferlins |
| Authors: |
Redpath, Gregory M. I.; Sophocleous, Reece A.; Turnbull, Lynne; Whitchurch, Cynthia B.; Cooper, Sandra T. |
| Contributors: |
Jain Foundation; University of Sydney |
| Source: |
Traffic ; volume 17, issue 3, page 245-266 ; ISSN 1398-9219 1600-0854 |
| Publisher Information: |
Wiley |
| Publication Year: |
2016 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/tra.12370 |
| Availability: |
https://doi.org/10.1111/tra.12370; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Ftra.12370; https://onlinelibrary.wiley.com/doi/pdf/10.1111/tra.12370 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.B95B1300 |
| Database: |
BASE |