title: Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle.
abstract: Filamin C is the muscle isoform of a group of large actin-crosslinking proteins. On the one hand, filamin C is associated with the Z-disk of the myofibrillar apparatus and binds to myotilin; on the other hand, it interacts with the sarcoglycan complex at the sarcolemma. Filamin C may be involved in reorganizing the cytoskeleton in response to signalling events and in muscle it may, in addition, fulfill structural functions at the Z-disk. An examination of biopsies from patients with multi-minicore myopathy, central core myopathy and neurogenic target fibers with core-like target formations (TF) revealed strong reactivity of all the cores and target formations with two different anti-filamin C antibodies. In all three conditions, the immunoreactivity in the cores for filamin C was considerably stronger than that for desmin. Only for alphaB-crystallin were comparable levels of immunoreactivity detected. There was no difference in intensity for filamin C between the three pathological conditions. Thus, filamin C along with alphaB-crystallin is a strong and robust, but nonspecific marker of core formation. The reason why filamin C accumulates in cores is unclear at present, but we postulate that it may be critically involved in the chain of events eventually leading to myofibrillar degeneration.
authors.affiliation: Division of Neurology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, 34th Strteet and Civic Center Boulevard, Philadelphia, PA 19104, USA. bonnemann@email.chop.edu
authors.forename: C G
authors.initials: CG
authors.lastname: Bönnemann
authors.forename: T G
authors.initials: TG
authors.lastname: Thompson
authors.forename: P F M
authors.initials: PF
authors.lastname: van der Ven
authors.forename: H H
authors.initials: HH
authors.lastname: Goebel
authors.forename: I
authors.initials: I
authors.lastname: Warlo
authors.forename: B
authors.initials: B
authors.lastname: Vollmers
authors.forename: J
authors.initials: J
authors.lastname: Reimann
authors.forename: J
authors.initials: J
authors.lastname: Herms
authors.forename: M
authors.initials: M
authors.lastname: Gautel
authors.forename: F
authors.initials: F
authors.lastname: Takada
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
authors.forename: D O
authors.initials: DO
authors.lastname: Fürst
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: F
authors.initials: F
authors.lastname: Hanefeld
authors.forename: R
authors.initials: R
authors.lastname: Schröder
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology*; D009135:Muscular Diseases / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D020033:Protein Isoforms