The ferlin protein family regulates membrane trafficking events for a wide range of cellular and physiological processes in eukaryotic organisms. Structurally, ferlins are distinguished by containing five to seven C2 domains with a single-pass transmembrane domain at the C-terminus. In mammals, there are 6 ferlin genes, including Fer1L6, which confer...
A fundamental difference between prokaryotic and eukaryotic cells is the presence of membrane bound organelles in eukaryotes. The dynamics of membrane trafficking within the cell are responsible for everything from intercellular communication and cell homeostasis, to mitosis, cell migration, and differentiation. These processes require exocytosis and compensatory endocytosis, often working...
Auditory defects and disorders are prevalent at all ages and affect 8% of the population in developed nations including newborns and children. Congenital hearing loss is the most common birth defect and it is estimated that 1 in 1000 children are affected by deafness at birth or before the onset...
Hearing loss is one of the most common defect, affecting 360 million people worldwide due to several factors including congenital, present at or soon after birth or acquired with age. Congenital hearing loss affects 32 million children in the world. The economic impact of hearing loss is estimated to cost...
Ferlins are a family of calcium-sensitive proteins involved in fusion and fission membrane trafficking events. There are six ferlin members: dysferlin, otoferlin, myoferlin, Fer1L4, Fer1L5, and Fer1L6. Previous research shows the first three ferlins play a pathophysiological role in humans, while the other three remain uncharacterized. Fer1L6 is one of...
Fer1L6 is an uncharacterized member of the ferlin family of proteins, a group of large, calcium sensitive proteins with emerging roles in vesicle trafficking and various disease states. The presence of Fer1L6 has been identified within the C2C12 cell line of mouse skeletal muscle. To determine the protein’s subcellular location...
Otoferlin is a protein that is essential in the process of hearing. Mutations in otoferlin are associated with profound recessive deafness. The long-term goal of the Johnson lab is to understand how otoferlin contributes to hearing and why certain mutations result in deafness. This project sought to characterize the difference...
Cell membranes act as barriers against unwanted movement of ions and biomolecules and are complex surfaces littered with protein channels, ion channels, cholesterol, and a myriad of different proteins. While this surface is extremely well studied, there is still much we do not know. The work in this dissertation demonstrates...
Dysferlin is a ∼230 kDa terminally anchored membrane protein that is ubiquitously expressed, but is particularly enriched in skeletal and cardiac muscle tissue. Mutations covering the length of the protein have been linked to muscle wasting diseases including limb-girdle muscular dystrophy and Myoshi myopathy. Dysferlin has been shown to play...
Congenital hearing loss is a common disorder and over 60 mutations in the sensory hair cell protein, otoferlin, have been linked to pre-lingual deafness. Although otoferlin is essential for hearing, the large size and low solubility of the protein have limited approaches to study its function on a molecular-level. To...