Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle

Bönnemann, C.G; Thompson, T.G; van der Ven, P.F.M; Goebel, H.H; Warlo, I; Vollmers, B; Reimann, J; Herms, J; Gautel, M; Takada, F; Beggs, A.H; Fürst, D.O; Kunkel, L.M; Hanefeld, F; Schröder, R

« Previous Next »Journal of the Neurological Sciences
Volume 206, Issue 1 , Pages 71-78, 15 January 2003

Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle

C.G Bönnemann
- Corresponding authors. C. Bönnemann is to be contacted at the Neuromuscular Program, Division of Neurology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel.: +1-215-590-7490; fax: +1-215-590-3709. R. Schröder, Tel.: +49-228-287-6805; fax: +49-228-287-6805.
- Division of Neurology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- Department of Neuropediatrics, University of Göttingen, Göttingen, Germany
T.G Thompson
- Division of Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA
P.F.M van der Ven
- Department of Cell Biology, University of Potsdam, Potsdam, Germany
H.H Goebel
- Department of Neuropathology, University of Mainz, Mainz, Germany
I Warlo
- Department of Neuropathology, University of Mainz, Mainz, Germany
B Vollmers
- Department of Neuropediatrics, University of Göttingen, Göttingen, Germany
J Reimann
- Department of Neurology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany
J Herms
- Department of Neuropathology, Ludwigs-Maximilians University, München, Germany
M Gautel
- Muscle Cell Biology, The Randall Centre, Kings College, London, UK
F Takada
- Division of Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA
A.H Beggs
- Division of Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA
D.O Fürst
- Department of Cell Biology, University of Potsdam, Potsdam, Germany
L.M Kunkel
- Division of Genetics, Children's Hospital and Harvard Medical School, Boston, MA, USA
F Hanefeld
- Department of Neuropediatrics, University of Göttingen, Göttingen, Germany
R Schröder
- Corresponding authors. C. Bönnemann is to be contacted at the Neuromuscular Program, Division of Neurology, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel.: +1-215-590-7490; fax: +1-215-590-3709. R. Schröder, Tel.: +49-228-287-6805; fax: +49-228-287-6805.
- Department of Neurology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany

Received 1 March 2002; received in revised form 21 June 2002; accepted 28 August 2002.

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 αB-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 αB-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.

Keywords: Cores, Filamin C, αB-crystallin, Congenital myopathies, Multi-minicore disease, Central core disease, Target formations

Abbreviations: CCD, central core disease, MmD, multi-minicore disease, TF, target formations