Abstract
Ferlins are multiple-C2-domain proteins involved in Ca2+-triggered membrane dynamics within the secretory, endocytic and lysosomal pathways. In bony vertebrates there are six ferlin genes encoding, in humans, dysferlin, otoferlin, myoferlin, Fer1L5 and 6 and the long noncoding RNA Fer1L4. Mutations in DYSF (dysferlin) can cause a range of muscle diseases with various clinical manifestations collectively known as dysferlinopathies, including limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy. A mutation in MYOF (myoferlin) was linked to a muscular dystrophy accompanied by cardiomyopathy. Mutations in OTOF (otoferlin) can be the cause of nonsyndromic deafness DFNB9. Dysregulated expression of any human ferlin may be associated with development of cancer. This review provides a detailed description of functions of the vertebrate ferlins with a focus on muscle ferlins and discusses the mechanisms leading to disease development.
Highlights
IntroductionFerlins belong to the superfamily of proteins with multiple C2 domains (MC2D) that share common functions in tethering membrane-bound organelles or recruiting proteins to cellular membranes
Ferlins belong to the superfamily of proteins with multiple C2 domains (MC2D) that share common functions in tethering membrane-bound organelles or recruiting proteins to cellular membranes.Ferlins are described as calcium ions (Ca2+ )-sensors for vesicular trafficking capable of sculpturing membranes [1,2,3]
Otoferlin is important for hearing in all studied bony vertebrates, its deficiency leads to profound nonsyndromic deafness in humans, profound hearing loss in mice accompanied by a mild vestibular deficit, and a hearing defect in zebrafish coexisting with a more prominent balance and locomotion dysfunction [6,25,26,142]
Summary
Ferlins belong to the superfamily of proteins with multiple C2 domains (MC2D) that share common functions in tethering membrane-bound organelles or recruiting proteins to cellular membranes. Ca2+ -sensors and organizers of vesicular trafficking, signaling, lipid transfer and as enzymes for lipid modification To fulfill these functions, MC2D proteins tether membranous organelles or recruit proteins to membranes. The scaffolding proteins Piccolo, RIM1 and RIM2 (Ras-related in brain 3 (Rab3)-interacting molecules) participate in the organization of the presynaptic active zone and recruitment of synaptic vesicles (SVs) to the membrane [13,14,15]. Mediate tethering of the ER to the plasma membrane (PM) and lipid transfer (extended synaptotagmins) [27], Recruit proteins to membranes and are involved in cell signaling (copines and RASAL1) [28–. MC2D proteins perform diverse functions and many of them control vesicular trafficking, in particular, neurotransmitter release, in one or the other way
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
