title: The formin FHOD1 in cardiomyocytes.
abstract: Members of the formin family are known to be involved in the regulation of the actin cytoskeleton. We have recently identified a muscle specific splice variant of the formin FHOD3 and demonstrated its role in the maintenance of the contractile filaments of cardiomyocytes. Here, we characterize the expression and subcellular localization of FHOD3's closest relative, FHOD1, in the heart. Confocal microscopy shows that FHOD1 is mainly located at the intercalated disc, the special type of cell-cell contact between cardiomyocytes, but also partially associated with the myofibrils. Subcellular targeting of FHOD1 is probably mediated by its N-terminal domain, since expression constructs lacking this domain show aberrant localization in primary cultures of neonatal rat cardiomyocytes. Finally, we show that in contrast to FHOD3, FHOD1 shows increased expression levels in dilated cardiomyopathy, suggesting that the two formins play distinct roles and are differentially regulated in cardiomyocytes.
authors.affiliation: Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, SE1 1UL, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dwyer
authors.forename: Marlene
authors.initials: M
authors.lastname: Pluess
authors.forename: Thomas
authors.initials: T
authors.lastname: Iskratsch
authors.forename: Cristobal G
authors.initials: CG
authors.lastname: Dos Remedios
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017208:Rats, Wistar; D014162:Transfection; D015854:Up-Regulation
chemical_list: C120021:FHOD1 protein, human; C586375:FHOD1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; C090114:cysteine and glycine-rich protein 3
keywords: actin; formin; intercalated disc; sarcomere