Dystonin/Bpag1—A link to what?

Abstract

The dystonin/Bpag1 cytoskeletal interacting proteins play important roles in maintaining cytoarchitecture integrity in skin and in the neuromuscular system. The most profound phenotype observed in the dystonin mutant dystonia musculorum (dt) mice is a severe movement disorder, attributed in large part to sensory neuron degeneration. The molecular basis for this phenotype is currently not clear, despite several studies indicating possible causes for the pathology in dt

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

“…The underlying mechanisms remain inconclusive and were proposed to be associated with roles of dystonin in intermediate filament organisation and axonal transport, and in ER or Golgi dysfunction (Ferrier et al, 2013;Young and Kothary, 2007). We propose instead that HSAN pathology might be primarily caused by defects in MT guidance and stabilisation on the basis of the following argument.…”

Functional and Genetic Analysis of Spectraplakins in Drosophila

“…For example, the epidermal isoform of BPAG1/dystonin is an important constituent of hemidesmosomes in basal epithelial layers, particularly in the skin where autoimmune or hereditary functional aberration causes skin blistering of The N-terminus of Dystonin-a2 promotes localization to the nuclear envelope (Young & Kothary, 2007;Young et al, 2003). Two calponin homology domains (CH1 and CH2) form a classical actin-binding domain (ABD) essential for neuronal morphogenesis (Alves-Silva et al, 2012;Jefferson, Leung, & Liem, 2004;Kodama, Lechler, & Fuchs, 2004;Lee & Kolodziej, 2002b;Leung, Sun, Zheng, Knowles, & Liem, 1999).…”

“…the epidermolysis bullosa simplex type (Aumailley et al, 2006). Functional loss of the longer isoforms in humans as well as mice causes severe postnatal neurodegeneration classified as hereditary sensory and autonomic neuropathy type VI (HSAN6; Edvardson et al, 2012: #6627;Ferrier, Boyer, & Kothary, 2013;Young & Kothary, 2007). Furthermore, patient studies suggest potential roles in neural development (Giorda et al, 2004;Vincent et al, 2008), human melanoma (Shimbo et al, 2010), and the infection process of Herpes virus (Pasdeloup, McElwee, Beilstein, Labetoulle, & Rixon, 2013).…”

Role of non-motile microtubule-associated proteins in virus trafficking

“…They possess a small four-residue motif, Ser-x-Ile-Pro (SxIP, where x denotes any amino acid), which is specifically recognized by the EBH domain of EB proteins (49). Dystonin is a giant protein that can interact with all three elements of the cytoskeleton, intermediate filaments, actin and MTs, via a N-terminal actin-binding domain and a C-terminal MT-binding domain (50). Four major isoforms (Dystonin a, b, e and n) have been identified to date, with differential tissue expression and resulting from alternative splicing patterns.…”